Combination of substituted 4-aminoisoindoline-1,3-dione compounds and second active agents for use in the treatment of a hematologic malignancy

Abstract

This document provides methods for using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopologue, or pharmaceutically acceptable salt thereof, in combination with a second active agent for the treatment, prevention, or control of hematological malignancies.The second active agent is one or more of the following: an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, an SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, a NEK2 inhibitor, a MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or chemotherapy.

Description

Combination of substituted 4-aminoisoindoline-1,3-dione compounds and second active agents for use in the treatment of a hematologic malignancy This application claims priority over U.S. Provisional Application No. 62 / 923,945, filed on October 21, 2019. 1. FIELD Methods are provided herein for using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof, in combination with a second active agent to treat, prevent, or control hematologic malignancies. 2. BACKGROUND Cancer is primarily characterized by an increase in the number of abnormal cells derived from a given normal tissue, the invasion of adjacent tissues by these abnormal cells, or the lymphatic or hematogenous spread of malignant cells to regional lymph nodes and metastasis. Clinical data and molecular biology studies indicate that cancer is a multi-step process that begins with minor preneoplastic changes, which under certain conditions can progress to neoplasia. The neoplastic lesion can evolve clonally and develop an increasing capacity for invasion, growth, metastasis, and heterogeneity, especially under conditions in which neoplastic cells escape the host's immune surveillance. Current cancer therapy may include surgery, chemotherapy, hormonal therapy, and / or radiation therapy to eradicate neoplastic cells in a patient.Recent advances in cancer therapeutic agents are discussed in Rajkumar et al. in Nature Reviews Clinical Oncology 11, 628-630 (2014). All current cancer treatment approaches present significant drawbacks for the patient. Surgery, for example, may be contraindicated due to the patient's health condition or may be unacceptable to the patient. Furthermore, surgery may not completely remove the cancerous tissue. Radiation therapy is only effective when the cancerous tissue is more sensitive to radiation than normal tissue. Radiation therapy also commonly causes serious side effects. Hormone therapy is rarely administered as a single agent. Although hormone therapy can be effective, it is often used to prevent or delay cancer recurrence after other treatments have eliminated most of the cancer cells. Despite the availability of a variety of chemotherapeutic agents, chemotherapy has many drawbacks. Almost all chemotherapeutic agents are toxic, and chemotherapy causes significant and often dangerous side effects, including severe nausea, bone marrow suppression, and immunosuppression. Furthermore, even with the administration of combinations of chemotherapeutic agents, many tumor cells are resistant or develop resistance to them. In fact, cells resistant to the particular chemotherapeutic agents used in the treatment protocol often turn out to be resistant to other drugs, even if those agents act through a different mechanism than the drugs used in the specific treatment. This phenomenon is called pleiotropic drug resistance or multidrug resistance.Due to drug resistance, many cancers are or become refractory to standard chemotherapy treatment protocols. Hematologic malignancies are cancers that originate in hematopoietic tissue, such as bone marrow, or in cells of the immune system. Examples of hematologic malignancies include leukemia, lymphoma, and myeloma. More specific examples of hematologic malignancies include, but are not limited to, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple myeloma (MM), non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), T-cell lymphoma (TCL), Burkitt lymphoma (BL), chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), marginal zone lymphoma (MZL), and myelodysplastic syndromes (MDS). 3. SUMMARY The invention is set forth in the accompanying set of claims. Any reference in the description to treatment methods refers to the compounds, pharmaceutical compositions, and medicaments of the present invention for use in a method of treating the human (or animal) body by therapy (or for diagnosis). Methods are provided herein for using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione (Compound 1), or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing, or controlling hematologic malignancies, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g.,ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib), an Aurora kinase inhibitor (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631),a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin or dexamethasone). Compound 1, or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, is also collectively referred to as "Compound A". Also provided for use in the methods provided herein are pharmaceutical compositions formulated for administration by a suitable route and means, containing effective concentrations of a compound provided herein, for example, Compound A, and optionally comprising at least one pharmaceutical carrier. In one embodiment, the compound provided herein is Compound 1. In one embodiment, the pharmaceutical compositions deliver quantities of Compound A effective for the treatment of a hematologic malignancy provided herein in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver quantities of Compound A effective for the prevention of a hematologic malignancy provided herein in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver quantities of Compound A effective for the enhancement of a hematologic malignancy provided herein in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver quantities of Compound 1 effective for the treatment of a hematologic malignancy provided herein in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver quantities of Compound 1 effective for the prevention of a hematologic malignancy provided herein in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver quantities of Compound 1 effective for the enhancement of a hematologic malignancy provided herein in combination with the second active agent provided herein. In one realization, hematologic malignancy is acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple myeloma (MM), non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), T-cell lymphoma (TCL), Burkitt lymphoma (BL), chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), marginal zone lymphoma (MZL), or myelodysplastic syndromes (MDS). In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of AML in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of AML in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of AML in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of AML in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of AML in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of AML in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of ALL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of ALL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of ALL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of ALL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of ALL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of ALL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of MM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of MM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of MM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of MM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of MM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of MM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of NHL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of NHL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of NHL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of NHL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of NHL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of NHL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of DLBCL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of DLBCL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of DLBCL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of DLBCL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of DLBCL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of DLBCL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of Hodgkin's lymphoma (HL) in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of HL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of HL in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of LH in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of LH in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of LH in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of LCT in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of LCT in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of LCT in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of LCT in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of LCT in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of LCT in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of LB in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of LB in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of LB in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of LB in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of LB in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of LB in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of CLL / LPP in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of CLL / LPP in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of CLL / LPP in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of CLL / LPP in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of CLL / LPP in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of CLL / LPP in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of LZM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of LZM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of LZM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of LZM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of LZM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of LZM in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the treatment of MDS in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the prevention of MDS in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound A effective for the improvement of MDS in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the treatment of MDS in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the prevention of MDS in combination with the second active agent provided herein. In one embodiment, the pharmaceutical compositions deliver amounts of Compound 1 effective for the improvement of MDS in combination with the second active agent provided herein. The compounds or compositions provided herein, or pharmaceutically acceptable derivatives thereof, may be administered simultaneously, before or after the administration of each of them and one or more of the above therapies. These and other aspects of the subject matter provided herein will become evident after consulting the following detailed description. 4. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 shows the sensitivity of the proliferation of the LDCBG cell line to treatment with Compound 1, as measured by a Cell Titer Glo assay. FIG.2 shows a heat map of the additive (light gray) and synergistic (dark gray) scores of combined hematologic malignancy cell line treatments with Compound 1 and the second active agents. FIG.3 shows the antitumor activity of Compound 1 alone and in combination with 5-azacytidine in the WSU-DLCL2 (LDCBG) xenograft model. FIG.4 shows the antitumor activity of Compound 1 alone and in combination with tazemetostat in the WSU-DLCL2 (LDCBG) xenograft model. FIG. 5A, FIG. 5B and FIG. 5C show the antitumor activity of Compound 1 (at 3, 10 and 30 mg / kg respectively) alone and in combination with tazemetostat in the DB xenograft (LDCBG) model. FIG.6 shows a heat map of the normalized percentage of tumor cells treated with Compound 1 in combination with venetoclax. FIG.7 shows the heat map of the normalized percentage of tumor cells treated with Compound 1 in combination with ibrutinib. FIG.8 shows the heat map of the additive and synergistic score of the combined treatments of LDCBG cell lines with Compound 1 and Compound B. 5. DETAILED DESCRIPTION OF THE INVENTION 5.1 Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person skilled in the art. In the event that there are multiple definitions for a term herein, unless otherwise indicated, the definitions in this section shall prevail. As used herein, in the descriptive memorandum and in the accompanying claims, the indefinite articles "a" and "one" and the definite article "the" include both plural and singular references, unless the context clearly indicates otherwise. As used herein, the terms "comprising" and "including" may be used interchangeably. It is to be understood that the terms "comprising" and "including" specify the presence of the features or components described, but do not exclude the presence or addition of one or more additional features, components, or groups thereof. Furthermore, the terms "comprising" and "including" are intended to encompass examples covered by the term "consisting of." Accordingly, the term "consisting of" may be used instead of the terms "comprising" and "including" to provide more specific embodiments of the invention. The term "consisting of" means that a material has at least 90%, 95%, 97%, 98%, or 99% of the stated characteristics or components comprising it. In any other embodiment, the term "consisting of" excludes from the scope of any further enumeration any other characteristics or components, except those that are not essential to the desired technical effect. As used herein, the term "or" should be interpreted as an inclusive "or" meaning any one or any combination. Thus, "A, B, or C" means any of the following: "A; B; C; A and B; A and C; B and C; A, B, and C." An exception to this definition will only occur when a combination of elements, functions, steps, or acts is in some way inherently mutually exclusive. As used herein, and unless otherwise specified, the terms "approximately" and "around," when used in relation to doses, amounts, or weight percentages of ingredients in a composition or dosage form, mean a dose, amount, or weight percentage that a person skilled in the art recognizes as capable of producing a pharmacological effect equivalent to that obtained with the specified dose, amount, or weight percentage. In certain embodiments, the terms "approximately" and "around," when used in this context, encompass a dose, amount, or weight percentage within 30%, 20%, 15%, 10%, or 5% of the specified dose, amount, or weight percentage. As used herein, and unless otherwise specified, the term "pharmaceutically acceptable salts" refers to salts prepared from relatively non-toxic, pharmaceutically acceptable acids, including inorganic acids and organic acids.In certain embodiments, suitable acids include, but are not limited to, acetic, adipic, 4-aminosalicylic, ascorbic, aspartic, benzenesulfonic, benzoic, camphoric, camphorsulfonic, capric, caproic, caprylic, cinnamic, carbonic, citric, cyclamic, dihydrogenphosphoric, 2,5-dihydroxybenzoic (gentisic), 1,2-ethanendisulfonic, ethanesulfonic, fumaric, galacturonic, gluconic, glucuronic, glutamic, glutaric, glycolic, hippuric, hydrobromic, hydrochloric, hydroiodic, isobutyric, isethonic, lactic, maleic, malic, malonic, mandelic, methanesulfonic, monohydrogencarbonic, monohydrogenphosphoric, monohydrogensulfuric, mucic, 1, 5-naphthalenedisulfonic, nicotinic, nitric, oxalic, pamoic, pantothenic, phosphoric, phthalic, propionic, pyroglutamic, salicylic, suberic, succinic, sulfuric, tartaric, toluenesulfonic and the like (see, for example, SM Berge et al., J. Pharm. Sci., 66:1-19 (1977); and Handbook of Pharmaceutical Salts: Properties, Selection and Use, PH Stahl and CG Wermuth, Eds., (2002), Wiley, Weinheim). In certain embodiments, suitable acids are strong acids (e.g., with a pKa of less than approximately 1) including, but not limited to, hydrochloric, hydrobromic, sulfuric, nitric, methanesulfonic, benzenesulfonic, toluenesulfonic, naphthalenesulfonic, naphthalenedisulfonic, pyridinesulfonic, or other substituted sulfonic acids. Also included are salts of other relatively nontoxic compounds that possess acidic character, including amino acids, such as aspartic acid and the like, and other compounds, such as aspirin, ibuprofen, saccharin, and the like. Acid addition salts can be obtained by contacting the neutral form of a compound with a sufficient quantity of the desired acid, either pure or in a suitable solvent. As used herein, and unless otherwise specified, the term "prodrug" of an active compound refers to compounds that are transformed in vivo to produce the active compound or a pharmaceutically acceptable form of the active compound. A prodrug may be inactive when administered to a subject but is converted in vivo to an active compound, for example, by hydrolysis (e.g., hydrolysis in the blood). Prodrugs include compounds in which a hydroxy, amino, or mercapto group is attached to any group that, when the prodrug of the active compound is administered to a subject, is cleaved to form a free hydroxy, free amino, or free mercapto group, respectively. As used herein, and unless otherwise specified, the term "isomer" refers to different compounds having the same molecular formula. "Stereoisomers" are isomers that differ only in the spatial arrangement of their atoms. "Atropisomers" are stereoisomers that arise from restricted rotation around single bonds. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A mixture of a pair of enantiomers in any proportion may be called a "racemic" mixture. "Diastereomers" are stereoisomers having at least two asymmetric atoms, but which are not mirror images of each other. Absolute stereochemistry can be specified according to the Cahn-Ingold-Prelog RS system. When a compound is an enantiomer, the stereochemistry at each chiral carbon can be specified by R or S.Solved compounds whose absolute configuration is unknown may be designated (+) or (-) depending on the direction (dextrorotatory or levorotatory) in which they rotate plane-polarized light at the wavelength of the sodium D line. However, the sign of the optical rotation, (+) and (-), is not related to the absolute configuration of the molecule, R and S. Some of the compounds described herein contain one or more asymmetric centers and may therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined, in terms of absolute stereochemistry at each asymmetric atom, as (R)- or (S)-. The chemical entities, pharmaceutical compositions, and methods presented herein are intended to encompass all possible isomers, including racemic mixtures, optically pure forms, and intermediate mixtures.Optically active (R)- and (S)- isomers can be prepared, for example, using chiral synthons or chiral reagents, or resolved using conventional techniques. Stereoisomers may also include E and Z isomers, or a mixture thereof, and cis and trans isomers, or a mixture thereof. In some embodiments, a compound described herein is isolated as either an E or Z isomer. In other embodiments, a compound described herein is a mixture of E and Z isomers. "Tautomers" refers to isomeric forms of a compound that exist in equilibrium with each other. The concentrations of the isomeric forms will depend on the environment in which the compound is found and can differ depending, for example, on whether the compound is a solid or in an organic or aqueous solution. For example, in aqueous solution, pyrazoles can exist in the following isomeric forms, which are called tautomers of each other: It should also be noted that a compound described herein may contain non-natural proportions of atomic isotopes in one or more of the atoms. For example, compounds may be radiolabeled with radioactive isotopes such as tritium (H), iodine-125 (125I), sulfur-35 (35S), or carbon-14 (14C), or they may be isotopically enriched, as with deuterium (2H), carbon-13 (13C), or nitrogen-15 (15N). As used herein, an "isotopologist" is an isotopically enriched compound. The term "isotopically enriched" refers to an atom having an isotopic composition different from the naturally occurring isotopic composition of that atom. "Isotopically enriched" can also refer to a compound that contains at least one atom with an isotopic composition different from the naturally occurring isotopic composition of that atom. The term "isotopic composition" refers to the amount of each isotope present in a given atom.Radiolabeled and isotopically enriched compounds are useful as therapeutic agents, for example, cancer therapies, research reagents, for example, bonding assay reagents, and diagnostic agents, for example, in vivo imaging agents. It is intended that all isotopic variations of a compound described herein, whether radioactive or not, are encompassed within the scope of the embodiments provided herein. In some embodiments, isotopologues of a compound described herein are provided; for example, isotopologues enriched with deuterium, carbon-13, and / or nitrogen-15. As used herein, "deuterated" means a compound in which at least one hydrogen (H) has been substituted by deuterium (denoted by D or 2H), i.e., the compound is enriched with deuterium at at least one position. It should be noted that if there is a discrepancy between a represented structure and the name of that structure, greater importance will be given to the represented structure. As used herein and unless otherwise indicated, the term "treat" means to relieve, in whole or in part, a disorder, disease or condition, or one or more of the symptoms associated with a disorder, disease or condition, or to slow or stop the further progression or worsening of such symptoms, or to relieve or eradicate the cause or causes of the disorder, disease or condition itself. As used herein and unless otherwise indicated, the term "prevent" means a method of delaying and / or preventing the onset, recurrence, or spread, in whole or in part, of a disorder, disease, or condition; preventing a subject from acquiring a disorder, disease, or condition; or reducing the risk of a subject acquiring a disorder, disease, or condition. As used herein and unless otherwise indicated, the term "control" encompasses preventing the recurrence of a particular disease or disorder in a patient who has had it, prolonging the time that a patient who has had a disease or disorder remains in remission, reducing patient mortality rates, and / or maintaining a reduction in the severity or avoiding a symptom associated with the disease or condition being controlled. As used herein and unless otherwise indicated, the term "effective amount" in relation to a compound means an amount capable of treating, preventing or controlling a disorder, disease or condition, or the symptoms thereof. As used herein and unless otherwise stated, the term "subject" or "patient" includes an animal, which includes, but is not limited to, an animal such as a cow, a monkey, a horse, a sheep, a pig, a chicken, a turkey, a quail, a cat, a dog, a mouse, a rat, a rabbit or a guinea pig, in one embodiment a mammal, in another embodiment a human being. As used herein, and unless otherwise indicated, the term "relapse" refers to a disorder, disease, or condition that responded to treatment (e.g., achieved a complete response) and then progressed. Treatment may include one or more lines of therapy. In one embodiment, the disorder, disease, or condition has been previously treated with one or more lines of therapy. In another embodiment, the disorder, disease, or condition has been previously treated with one, two, three, or four lines of therapy. In some embodiments, the disorder, disease, or condition is a hematologic malignancy. In one embodiment, "relapsed" LDCBG may refer to LDCBG that has been previously treated with one or more lines of therapy. In one embodiment, relapsed LDCBG is LDCBG that has been previously treated with one, two, three, or four lines of therapy. In one embodiment, relapsed LDCBG is LDCBG that has been previously treated with two or more lines of treatment. As used herein, and unless otherwise indicated, the term "refractory" refers to a disorder, disease, or condition that has not responded to prior treatment, which may include one or more lines of therapy. In one embodiment, the disorder, disease, or condition has been previously treated with one, two, three, or four lines of therapy. In another embodiment, the disorder, disease, or condition has been previously treated with two or more lines of treatment and has a less than complete response (CR) to the regimen containing the most recent systemic therapy. In some embodiments, the disorder, disease, or condition is a hematologic malignancy. In one embodiment, "relapsed or refractory" CLL / PLS may refer to CLL / PLS that has been previously treated with one or more lines of therapy. In one embodiment, relapsed or refractory CLL / PLS is CLL / PLS that has been previously treated with one, two, three, or four lines of therapy. In one embodiment, relapsed or refractory CLL / PLS is CLL / PLS that has been previously treated with two or more lines of therapy. In one embodiment, relapsed or refractory CLL / PLS is CLL / PLS that has been previously treated with a Bruton's tyrosine kinase (BTK) inhibitor. In one embodiment, relapsed or refractory CLL / PLS is relapsed or refractory to a BTK inhibitor. In one embodiment, the BTK inhibitor is ibrutinib. In one embodiment, the BTK inhibitor is acalabrutinib. In one embodiment, the BTK inhibitor is zanubrutinib. In another embodiment, the BTK inhibitor is tirabrutinib. In the context of cancer, for example, a hematologic malignancy, inhibition can be assessed by inhibiting disease progression, inhibiting tumor growth, reducing the primary tumor, alleviating tumor-related symptoms, inhibiting tumor-secreted factors, delaying the onset of primary or secondary tumors, slowing the development of primary or secondary tumors, decreasing the occurrence of primary or secondary tumors, slowing or decreasing the severity of disease side effects, arresting tumor growth and regressing tumors, increasing time to progression (TTP), increasing progression-free survival (PFS), and increasing overall survival (OS), among others. OS, as used herein, refers to the time elapsed from the start of treatment until death from any cause.Time to treatment (TTP), as used herein, refers to the time from the start of treatment to tumor progression; TTP does not include deaths. In one embodiment, time to failure (TPF) refers to the time from the start of treatment to tumor progression or death. In one embodiment, TPF refers to the time from the first dose of the compound to the first occurrence of disease progression or death from any cause. In one embodiment, TPF rates are calculated using Kaplan-Meier estimates. Event-free survival (EFS) refers to the time from the start of treatment to any treatment failure, including disease progression, discontinuation of treatment for any reason, or death. In one embodiment, overall response rate (ORR) refers to the percentage of patients who achieve a response.In one realization, ORR refers to the sum of the percentage of patients who achieve complete and partial responses. In one realization, ORR refers to the percentage of patients whose best response is a partial response (PR). In one realization, duration of response (DoR) is the time elapsed from achieving a response until relapse or disease progression. In one realization, DoR is the time elapsed from achieving a partial response (PR) until relapse or disease progression. In one realization, DoR is the time elapsed from the first documentation of a response until the first documentation of progressive disease or death. In one realization, DoR is the time elapsed from the first documentation of a partial response (PR) until the first documentation of progressive disease or death.In one embodiment, time to response (TTR) refers to the time elapsed from the first dose of the compound to the first documented response. In another embodiment, TTR refers to the time elapsed from the first dose of the compound to the first documented partial response (PR). At the extreme, complete inhibition is referred to herein as prevention or chemoprevention. In this context, the term "prevention" includes both the complete prevention of the development of clinically evident cancer and the prevention of the development of a preclinically evident stage of cancer. This definition is also intended to include the prevention of transformation into malignant cells or the arrest or reversal of the progression of premalignant cells to malignant cells. This includes the prophylactic treatment of those at risk of developing cancer. In certain realizations, NHL treatment can be evaluated using the International Workshop Criteria for Malignant Lymphoma (see Cheson et al., J Cin. Oncol. 2014, 32 (27):3059-3068) and the Deauville Criteria for the interpretation of fluorodeoxyglucose positron emission tomography (FDG-PET) (Itti et al., Eur. J. Nuc. Med. Mol. Imaging, 2013, 40 (9):1312-20; Meignan et al., Leuk Lymphoma, 2014, 55 (1):31-37) ("Lugano criteria"), using the response definition and assessment criteria shown in Tables 1-3. Table 1. Criteria for site impact. Table 2. Lugano response criteria for non-Hodgkin lymphoma. (continuation) (continuation) (continuation) PET / CT Site Response (Metabolic Response) CT (Radiological Response) CMR = complete metabolic response; LDi = longest transverse diameter of a lesion; PPD = cross product of LDi and perpendicular diameter; SDi = shortest axis perpendicular to LDi; SPD = sum of the product of perpendicular diameters for multiple lesions; N / A = not applicable. ª Required for CR if there is bone marrow involvement at baseline. b In Waldeyer's ring or in extranodal sites with high physiological uptake or activation within the spleen or bone marrow (e.g., with chemotherapy or myeloid colony-stimulating factors), uptake may be greater than in the normal mediastinum and / or liver. In this circumstance, MRC may be inferred if uptake at the initial sites of involvement is not greater than in the surrounding normal tissue. c FDG-avid lymphomas should be evaluated by PET-CT. Some diseases can typically be followed with CT alone (e.g., marginal zone lymphoma). d PET should be performed with a diagnostic CT scan with contrast and can be performed simultaneously or in separate procedures. Table 3. PET Five-Point Scale (5-PS). In one realization, the response to treatment of CLL / CLL can be assessed using the International Workshop on Chronic Lymphocytic Leukemia Criteria (see Hallek, M, et al. iwCLL Guidelines for diagnosis, treatment indications, response assessment and supportive care of CLL. Blood, 131 (25), 2745-2760 (2018)) (Table 4). Table 4. Definition of response after treatment in patients with chronic lymphocytic leukemia. (continuation) In one embodiment, the response to CLL / LLP treatment can be assessed by the Eastern Cooperative Oncology Group (ECOG) functional status (Table 5). Table 5. ECOG functional status. (continuation) In certain realizations, stable disease or the absence thereof can be determined by methods known in the technique, such as assessment of the patient's symptoms, physical examination, visualization of the tumor from which images have been obtained, for example using FDG-PET (fluorodeoxyglucose positron emission tomography), PET / CT (positron emission tomography / computed tomography), MRI (magnetic resonance imaging) of the brain and spine, cerebrospinal fluid (CSF), ophthalmological examinations, vitreous fluid sampling, retinal photography, bone marrow assessment, and other commonly accepted assessment modalities. As used herein and unless otherwise stated, the terms "co-administration" and "in combination with" include the administration of one or more therapeutic agents (e.g., a compound provided herein and another anticancer agent or adjunctive treatment agent) simultaneously, concurrently, or sequentially without any specific time limits. In one embodiment, the agents are present in the patient's cell or body at the same time or exert their biological or therapeutic effect at the same time. In one embodiment, the therapeutic agents are in the same composition or unit dosage form. In another embodiment, the therapeutic agents are in separate compositions or unit dosage forms. The term "adjunctive treatment agent" refers to any substance that treats, prevents, or controls an adverse effect resulting from treatment with another therapeutic agent. 5.2 Compound 1 For use in the methods provided herein, the compound (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, referred to as "Compound 1", is provided: or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. The methods of preparation of Compound 1 are described in U.S. Application No. 16 / 390, 815. Compound 1, or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof, is also collectively referred to as "Compound A". In one embodiment, the methods provided herein use the free base of Compound 1. In one embodiment, the methods provided herein use a pharmaceutically acceptable salt of Compound 1. In one embodiment, the methods provided herein use a hydrochloride salt of Compound 1. In one embodiment, the methods provided herein use one enantiomer of Compound 1 (for example, the R enantiomer of Compound 1). In another embodiment, the methods provided herein use a mixture of enantiomers of Compound 1 (for example, the racemic compound of Compound 1). In one embodiment, the methods provided herein use a tautomer of Compound 1. In one embodiment, the methods provided herein use an isotopologue of Compound 1. 5.3 Second active agents

[0077] In one embodiment, the second active agent used in the methods provided herein is a histone deacetylase (HDAC) inhibitor. In one embodiment, the HDAC inhibitor is panobinostat, romidepsin, vorinostat, or cytarinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the HDAC inhibitor is panobinostat, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the HDAC inhibitor is panobinostat. In one embodiment, the HDAC inhibitor is a pharmaceutically acceptable salt of panobinostat. In one embodiment, the HDAC inhibitor is panobinostat lactate. In one embodiment, the HDAC inhibitor is a monolactate salt of panobinostat. Panobinostat has the chemical name (2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]acrylamide, and has the structure: In one embodiment, the HDAC inhibitor is romidepsin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the HDAC inhibitor is romidepsin. Romidepsin has the chemical name (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]tric-16-ene-3,6,9,19,22-pentone, and has the structure: In one embodiment, the HDAC inhibitor is vorinostat, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. Vorinostat has the chemical name N-hydroxy-N-phenyloctanediamide and the structure: In one embodiment, the HDAC inhibitor is an HDAC6 inhibitor. In one embodiment, the HDAC6 inhibitor is cytarinostat, or a tautomer, isotope, or pharmaceutically acceptable salt thereof. In one embodiment, the HDAC6 inhibitor is cytarinostat. Cytarinostat (also known as ACY-241) has the chemical name 2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an inhibitor of B-cell lymphoma protein 2 (BCL2). In one embodiment, the BCL2 inhibitor is venetoclax, or a pharmaceutically acceptable tautomer, isotope, or salt thereof. In one embodiment, the BCL2 inhibitor is venetoclax. Venetoclax has the chemical name 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyrano-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a Bruton's tyrosine kinase (BTK) inhibitor. In one embodiment, the BTK inhibitor is ibrutinib, or acalabrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BTK inhibitor is ibrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BTK inhibitor is ibrutinib. Ibrutinib has the chemical name 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one, and has the structure: In one embodiment, the BTK inhibitor is acalabrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotope, or a pharmaceutically acceptable salt thereof. In one embodiment, the BTK inhibitor is acalabrutinib. Acalabrutinib has the chemical name (S)-4-(8-amino-3-(1-(but-2-inoyl)pyrrolidine-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridine-2-yl)benzamide, and has the following structure: In one embodiment, the second active agent used in the methods provided herein is a mammalian target of rapamycin (mTOR) inhibitor. In one embodiment, the mTOR inhibitor is rapamycin or an analogue thereof (also called a rapalog). In one embodiment, the mTOR inhibitor is everolimus, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the mTOR inhibitor is everolimus. Everolimus has the chemical name 40-O-(2-hydroxyethyl)-rapamycin and has the structure: In one embodiment, the second active agent used in the methods provided herein is a phosphoinositide 3-kinase (PI3K) inhibitor. In one embodiment, the PI3K inhibitor is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PI3K inhibitor is idelalisib. Idelalisib has the chemical name 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a protein kinase C beta (PKCβ or PKC-β) inhibitor. In one embodiment, the PKCβ inhibitor is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PKCβ inhibitor is enzastaurin. In one embodiment, the PKCβ inhibitor is a pharmaceutically acceptable salt of enzastaurin. In one embodiment, the PKCβ inhibitor is an enzastaurin hydrochloride salt. In one embodiment, the PKCβ inhibitor is an enzastaurin bis-hydrochloride salt. Enzastaurin has the chemical name 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a spleen tyrosine kinase (SYK) inhibitor. In one embodiment, the SYK inhibitor is fostamatinib, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the SYK inhibitor is fostamatinib. In one embodiment, the SYK inhibitor is a pharmaceutically acceptable salt of fostamatinib. In one embodiment, the SYK inhibitor is fostamatinib disodium hexahydrate. Fostamatinib (also known as R788) has the chemical name (6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-3-oxo-2,3-dihydro-4H-pyrido[3,2-b][1,4]oxazin-4-yl)methyl dihydrogen phosphate, and has the following structure: In one embodiment, the second active agent used in the methods provided herein is a Janus kinase 2 (JAK2) inhibitor. In one embodiment, the JAK2 inhibitor is fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib, or a pharmaceutically acceptable stereoisomer, mixture of stereoisomers, tautomer, isotopologue, or salt thereof. In one embodiment, the JAK2 inhibitor is fedratinib, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. Fedratinib has the chemical name N-tert-butyl-3-[(5-methyl-2-{4-[2-(pyrrolididin-1-yl)ethoxy]anilino}pyrimidin-4-yl)amino]benzenesulfonamide, and has the structure: In one embodiment, the JAK2 inhibitor is pacritinib, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the JAK2 inhibitor is pacritinib. Pacritinib has the following structure: In one embodiment, the JAK2 inhibitor is ruxolitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the JAK2 inhibitor is ruxolitinib. In one embodiment, the JAK2 inhibitor is a pharmaceutically acceptable salt of ruxolitinib. In one embodiment, the JAK2 inhibitor is ruxolitinib phosphate. Ruxolitinib has the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile, and has the structure. In one embodiment, the second active agent used in the methods provided herein is an Aurora kinase inhibitor. In one embodiment, the Aurora kinase inhibitor is an Aurora kinase A inhibitor. In one embodiment, the Aurora kinase inhibitor is an Aurora kinase B inhibitor. In one embodiment, the Aurora kinase inhibitor is a pan-Aurora kinase inhibitor. In one embodiment, the Aurora kinase inhibitor is alisertib, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. Alisertib has the chemical name 4-((9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)-2-methoxybenzoic acid, and has the structure: In one embodiment, the Aurora kinase inhibitor is barasertib (also known as AZD1152) or AZD1152-HQPA, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the Aurora kinase inhibitor is barasertib. In one embodiment, the Aurora kinase inhibitor is AZD1152-HQPA. AZD1152-HQPA (also known as AZD2811) has the chemical name 2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide, and has the structure: Barasertib is a dihydrogen phosphate prodrug of AZD1152-HQPA and has the following structure: In one embodiment, the Aurora kinase inhibitor is danusertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the Aurora kinase inhibitor is danusertib. Danusertib (also known as PHA-739358) has the following structure: In one embodiment, the Aurora kinase inhibitor is AT9283, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. AT9283 has the following structure: In one embodiment, the Aurora kinase inhibitor is PF-03814735, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the Aurora kinase inhibitor is PF-03814735. PF-03814735 has the following structure: In one embodiment, the Aurora kinase inhibitor is AMG900, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. AMG900 has the following structure: In one embodiment, the Aurora kinase inhibitor is tozasertib, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. Tozasertib (also known as VX-680 or MK-0457) has the following structure: In one embodiment, the Aurora kinase inhibitor is ZM447439, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. ZM447439 has the following structure: In one embodiment, the Aurora kinase inhibitor is MLN8054, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. MLN8054 has the following structure: In one embodiment, the Aurora kinase inhibitor is hesperidine, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, the Aurora kinase inhibitor is hesperidine. In one embodiment, the Aurora kinase inhibitor is a hesperidine hydrochloride salt. Hesperadine has the structure: In one embodiment, the Aurora kinase inhibitor is SNS-314, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the Aurora kinase inhibitor is SNS-314. In one embodiment, the Aurora kinase inhibitor is a mesylate salt of SNS-314. SNS-314 has the following structure: In one embodiment, the Aurora kinase inhibitor is PHA-680632, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. PHA-680632 has the following structure: In one embodiment, the Aurora kinase inhibitor is CYC116, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. CYC116 has the following structure: In one embodiment, the Aurora kinase inhibitor is GSK1070916, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. GSK1070916 has the following structure: In one embodiment, the Aurora kinase inhibitor is TAK-901, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. TAK-901 has the following structure: In one embodiment, the Aurora kinase inhibitor is CCT137690, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. CCT137690 has the following structure: In one embodiment, the second active agent used in the methods provided herein is a Zeste homologue enhancer 2 (EZH2) inhibitor. In one embodiment, the EZH2 inhibitor is tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A (DZNep), EPZ005687, EI1, UNC1999, or sinefungin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the EZH2 inhibitor is tazemetostat, or a pharmaceutically acceptable tautomer, isotope, or salt thereof. Tazemetostat (also known as EPZ-6438) has the chemical name N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-5-[ethyl(tetrahydro-2H-pyrano-4-yl)amino]-4-methyl-4-(4-morpholinylmethyl)-[1,1-biphenyl]-3-carboxamide, and has the structure: In one embodiment, the EZH2 inhibitor is GSK126, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the EZH2 inhibitor is GSK126 (also known as GSK-2816126). GSK126 has the chemical name (S)-1-(sec-butyl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide, and has the structure: In one embodiment, the EZH2 inhibitor is CPI-1205, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the EZH2 inhibitor is CPI-1205. CPI-1205 has the chemical name (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide, and has the structure: In one embodiment, the EZH2 inhibitor is 3-deazaneplanoscin A. In one embodiment, the EZH2 inhibitor is EPZ005687. In one embodiment, the EZH2 inhibitor is EI1. In one embodiment, the EZH2 inhibitor is UNC1999. In one embodiment, the EZH2 inhibitor is sinefungin. In one embodiment, the second active agent used in the methods provided herein is a bromodomain and extra-terminal motif (BET) protein inhibitor. In one embodiment, the BET inhibitor is birabresib or Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BET inhibitor is birabresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BET inhibitor is birabresib. Birabresib (also known as OTX015 or MK-8628) has the chemical name (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide, and has the structure: In one embodiment, the BET inhibitor is Compound B, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. Compound B has the chemical name 4-[2-(cyclopropylmethoxy)-5-(methanesulfonyl)phenyl]-2-methylisquinolin-1(2H)-one, and has the structure: In one embodiment, the BET inhibitor is BMS-986158, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BET inhibitor is BMS-986158. BMS-986158 has the following structure: In one embodiment, the BET inhibitor is RO-6870810, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. RO-6870810 has the following structure: In one embodiment, the BET inhibitor is CPI-0610, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BET inhibitor is CPI-0610. CPI-0610 has the structure: In one embodiment, the BET inhibitor is molibresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BET inhibitor is molibresib. Molibresib (also known as GSK-525762) has the following structure: In one embodiment, the second active agent used in the methods provided herein is a hypomethylating agent. In one embodiment, the hypomethylating agent is a DNA methyltransferase inhibitor. In one embodiment, the hypomethylating agent is 5-azacitidine or decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. Unless otherwise specified, the terms "azacitidine" and "azacitidine" are used interchangeably. In one embodiment, the hypomethylating agent is 5-azacytidine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. 5-Azacytidine has the chemical name 4-amino-1-β-D-ribofuranosyl-1,3,5-triazine-2(1H)-one and has the structure: In one embodiment, the hypomethylating agent is decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the hypomethylating agent is decitabine. Decitabine has the chemical name 4-amino-1-(2-deoxy-β-D-erythropentofuranosyl)-1,3,5-triazine-2(1H)-one, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a telomere silencing disruptor type 1 (DOT1L) inhibitor. In one embodiment, the DOT1L inhibitor is pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the DOT1L inhibitor is pinometostat. Pinometostat (also known as EPZ-5676) has the chemical name (2R, 3R, 4S, 5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r, 3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol, and has the structure: In one embodiment, the DOT1L inhibitor is SGC0946, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the DOT1L inhibitor is SGC0946. SGC0946 has the chemical name 5-bromo-7-[5-deoxy-5-[[3-[[[[[4-(1,1-dimethylethyl)phenyl]amino]carbonyl]amino]propyl](1-methylethyl)amino]-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine-4-amine, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a histone acetyltransferase (HAT) inhibitor. In one embodiment, the HAT inhibitor is C646, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the HAT inhibitor is C646. C646 has the chemical name 4-(4-((5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl)methylene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid, and has the structure. In one embodiment, the second active agent used in the methods provided herein is an inhibitor of protein 5 containing WD repeats (WDR5). In one embodiment, the WDR5 inhibitor is OICR 9429, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the WDR5 inhibitor is OICR-9429. OICR-9429 has the chemical name N-(4-(4-methylpiperazin-1-yl)-3-(morpholinomethyl)-[1,1-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an inhibitor of DNA (cytosine-5)-methyltransferase 1 (DNMT1). In one embodiment, the DNMT1 inhibitor is a selective DNMT1 inhibitor. In one embodiment, the selective DNMT1 inhibitor is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the selective DNMT1 inhibitor is GSK3484862. GSK3484862 (also known as GSKMI-714) has the chemical name (R)-2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)-2-phenylacetamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a lysine-specific demethylase 1 (LSD-1) inhibitor. In one embodiment, the LSD-1 inhibitor is Compound C or seclidemstat, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the LSD-1 inhibitor is Compound C, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the LSD-1 inhibitor is Compound C. In one embodiment, the LSD-1 inhibitor is a pharmaceutically acceptable salt of Compound C. In one embodiment, the LSD-1 inhibitor is the besylate of Compound C. In one embodiment, the LSD-1 inhibitor is the mono-besylate of Compound C. Compound C has the chemical name 4-(2-(4-aminopiperidin-1-yl)-5-(3-fluoro-4-methoxyphenyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-2-fluorobenzonitrile, and has the structure: In one embodiment, the LSD-1 inhibitor is seclidemstat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, the LSD-1 inhibitor is seclidemstat. In one embodiment, the LSD-1 inhibitor is a pharmaceutically acceptable salt of seclidemstat. In one embodiment, the LSD-1 inhibitor is seclidemstat mesylate. Seclidemstat (also known as SP-2577) has the chemical name (E)-N-(1-(5-chloro-2-hydroxyphenyl)ethylidene)-3-((4-methylpiperazin-1-yl)sulfonyl)benzohydrazide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a G9A inhibitor (one of the histone H3 methyltransferases). In one embodiment, the G9A inhibitor is UNC0631, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the G9A inhibitor is UNC0631. UNC0631 has the chemical name N-(1-(cyclohexylmethyl)piperidin-4-yl)-2-(4-isopropyl-1,4-diazepan-1-yl)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an inhibitor of the protein arginine methyltransferase 5 (PRMT5). In one embodiment, the PRMT5 inhibitor is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PRMT5 inhibitor is GSK3326595. GSK3326595 (also known as EPZ-015938) has the chemical name (S)-6-((1-acetylpiperidin-4-yl)amino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)pyrimidine-4-carboxamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a bromodomain (BRD) inhibitor. In one embodiment, the BRD inhibitor is a BRD9 / 7 inhibitor. In one embodiment, the BRD9 / 7 inhibitor is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BRD9 / 7 inhibitor is LP99. LP99 has the chemical name N-((2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxo-1,2-dihydroquinolin-7-yl)-6-oxopiperidin 3-yl)-2-methylpropane-1-sulfonamide, and has the structure: In one embodiment, the BRD inhibitor is a BRD4 inhibitor. In one embodiment, the BRD4 inhibitor is JQ1, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the BRD4 inhibitor is JQ1. JQ1 has the chemical name 2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)(S)-tert-butyl acetate, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an inhibitor of SUV420H1 / H2 (two homologous enzymes that methylate lysine 20 of histone H4). In one embodiment, the SUV420H1 / H2 inhibitor is A-196, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the SUV420H1 / H2 inhibitor is A-196. A-196 has the chemical name 6,7-dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazine-1-amine and has the structure: In one embodiment, the second active agent used in the methods provided herein is a coactivator-associated arginine methyltransferase 1 (CARM1) inhibitor. In one embodiment, the CARM1 inhibitor is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the CARM1 inhibitor is EZM2302. EZM2302 has the chemical name (R)-2-(2-(2-chloro-5-(2-hydroxy-3-(methylamino)propoxy)phenyl)-6-(3,5-dimethylisoxazol-4-yl)-5-methylpyrimidin-4-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a Polo-like kinase 1 (PLK1) inhibitor. In one embodiment, the PLK1 inhibitor is BI2536, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PLK1 inhibitor is BI2536. BI2536 has the chemical name (R)-4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide, and has the structure: In one embodiment, the PLK1 inhibitor is volasertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PLK1 inhibitor is volasertib. Volasertib (also known as BI6727) has the structure: In one embodiment, the PLK1 inhibitor is CYC140, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PLK1 inhibitor is onvansertib, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. Onvansertib (also known as NMS-1286937) has the following structure: In one embodiment, the PLK1 inhibitor is GSK461364, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PLK1 inhibitor is GSK461364. GSK461364 has the following structure: In one embodiment, the PLK1 inhibitor is TAK960, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, the PLK1 inhibitor is TAK960. In one embodiment, the PLK1 inhibitor is a hydrochloride salt of TAK960. TAK960 has the structure: In one embodiment, the second active agent used in the methods provided herein is a serine / threonine kinase (NEK2) inhibitor. In one embodiment, the NEK2 inhibitor is JH295, or a pharmaceutically acceptable tautomer, isotopologue, or salt thereof. In one embodiment, the NEK2 inhibitor is JH295. JH295 has the chemical name (Z)-N-(3-((2-ethyl-4-methyl-1H-imidazol-5-yl)methylene)-2-oxoindolin-5-yl)propionamide, and has the structure: In one embodiment, the NEK2 inhibitor is rac-CCT 250863, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the NEK2 inhibitor is rac-CCT 250863. Rac-CCT 250863 has the chemical name 4-[2-amino-5-[4-[(dimethylamino)methyl]-2-thienyl]-3-pyridinyl]-2-[[(2Z)-4,4,4-trifluoro-1-methyl-2-buten-1-yl]oxy]benzamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an inhibitor of mitogen-activated extracellular signal-regulated kinase (MEK). In one embodiment, the MEK inhibitor disrupts the function of the RAF / RAS / MEK signal transduction cascade. In one embodiment, the MEK inhibitor is trametinib, trametinib dimethyl sulfoxide, cobimetinib, binimetinib, or selumetinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the MEK inhibitor is trametinib. In one embodiment, the MEK inhibitor is trametinib dimethyl sulfoxide. In another embodiment, the MEK inhibitor is cobimetinib.In one embodiment, the MEK inhibitor is binimetinib. In another embodiment, the MEK inhibitor is selumetinib. Trametinib dimethyl sulfoxide has the chemical name N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide, compounded with dimethyl sulfoxide (1:1). Trametinib dimethyl sulfoxide has the following structure: In one embodiment, the second active agent used in the methods provided herein is an inhibitor of the PHD 19 finger protein (PH-F19). In one embodiment, the second active agent used in the methods provided herein is an inhibitor of the proviral integration site of Moloney murine leukemia kinase (PIM). In one embodiment, the PIM inhibitor is a pan-PIM inhibitor. In one embodiment, the PIM inhibitor is LGH-447, AZD1208, SGI-1776, or TP-3654, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PIM inhibitor is LGH-447, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the PIM inhibitor is LGH-447. In one embodiment, the PIM inhibitor is a pharmaceutically acceptable salt of LGH-447. In one embodiment, the PIM inhibitor is a hydrochloride salt of LGH-447. In another embodiment, the hydrochloride salt of LGH-447 is a dihydrochloride salt.In one embodiment, the hydrochloride salt of LGH-447 is a monohydrochloride salt. In one embodiment, the PIM inhibitor is AZD1208. In one embodiment, the PIM inhibitor is SGI-1776. In one embodiment, the PIM inhibitor is TP-3654. LGH-447 has the chemical name N-[4-[(1R,3S,5S)-3-amino-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoro-2-pyridincarboxamide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an insulin-like growth factor receptor 1 (IGF-1R) inhibitor. In one embodiment, the IGF-1R inhibitor is linsitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotope, or a pharmaceutically acceptable salt thereof. In one embodiment, the IGF-1R inhibitor is linsitinib. Linsitinib has the chemical name cis-3-[8-amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methylcyclobutanol, and has the structure: In one embodiment, the second active agent used in the methods provided herein is an exportin-1 (XPO1) inhibitor. In one embodiment, the XPO1 inhibitor is selinexor, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotope, or a pharmaceutically acceptable salt thereof. In one embodiment, the XPO1 inhibitor is selinexor. Selinexor has the chemical name (2Z)-3-{3-[3,5-bis(trifluoromethyl)phenyl]-1H-1,2,4-triazol-1-yl}-N-(pyrazin-2-yl)prop-2-enhydrazide, and has the structure: In one embodiment, the second active agent used in the methods provided herein is a survivin inhibitor (also called baculoviral apoptosis inhibitor-containing repeat 5 or BIRC5 protein). In one embodiment, the BIRC5 inhibitor is YM155, or a pharmaceutically acceptable tautomer, isotope, or salt thereof. In one embodiment, the BIRC5 inhibitor is YM155. YM155 has the chemical name 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazol-3-ium bromide and has the structure: In one embodiment, the second active agent used in the methods provided herein is a chemotherapy drug. In one embodiment, the chemotherapy drug is bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy is bendamustine, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy is bendamustine. In one embodiment, the chemotherapy is a pharmaceutically acceptable salt of bendamustine. In one embodiment, the chemotherapy is bendamustine hydrochloride. In one embodiment, the chemotherapy is a salt of bendamustine monohydrochloride. Bendamustine has the chemical name 4-(5-(bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid and has the structure: In one embodiment, the chemotherapy is doxorubicin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy is doxorubicin. In one embodiment, the chemotherapy is a pharmaceutically acceptable salt of doxorubicin. In one embodiment, the chemotherapy is doxorubicin hydrochloride. In one embodiment, the chemotherapy is a monohydrochloride salt of doxorubicin. Doxorubicin has the structure: In one embodiment, the chemotherapy drug is etoposide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy drug is etoposide. The etoposide has the chemical name 4-desmethylepipodophyllotoxin 9-[4,6-β-(R)-ethylideneβ-D-glucopyranoside] and has the structure: In one embodiment, chemotherapy is an etoposide prodrug. In one embodiment, chemotherapy is an etoposide ester prodrug. In one embodiment, chemotherapy is etoposide phosphate. Etoposide phosphate has the chemical name 4-desmethylepipodophyllotoxin 9-[4,6-β-(R)-ethylidene-β-D-glucopyranoside], 4-(dihydrogen phosphate), and has the structure: In one embodiment, the chemotherapy is methotrexate, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy is methotrexate. In one embodiment, the chemotherapy is a pharmaceutically acceptable salt of methotrexate. In one embodiment, the chemotherapy is sodium methotrexate. Methotrexate has the chemical name (4-(((2,4-diaminopteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamic acid and has the structure: In one embodiment, the chemotherapy agent is cytarabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy agent is cytarabine. Cytarabine has the chemical name 4-amino-1-β-D-arabinofuranosyl-2(1H)pyrimidinone and has the structure: In one embodiment, the chemotherapy is vincristine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy is vincristine. In one embodiment, the chemotherapy is a pharmaceutically acceptable salt of vincristine. In one embodiment, the chemotherapy is vincristine sulfate. In one embodiment, the chemotherapy is a vincristine monosulfate salt. Vincristine has the structure: In one embodiment, the chemotherapy agent is ifosfamide, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy agent is ifosfamide. Ifosfamide has the chemical name 3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide, and has the structure: In one embodiment, the chemotherapy is melphalan, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy is melphalan. In one embodiment, the chemotherapy is a pharmaceutically acceptable salt of melphalan. In one embodiment, the chemotherapy is melphalan hydrochloride. In one embodiment, the chemotherapy is a melphalan monohydrochloride salt. Melphalan has the chemical name 4-[bis(2-chloroethyl)amino]-L-phenylalanine and has the structure: In one embodiment, the chemotherapy agent is oxaliplatin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy agent is oxaliplatin. Oxaliplatin has the chemical name cis-[(1R,2R)-1,2-cyclohexanediamine-N,N][oxalato(2-)-O,O]platinum, and has the structure: In one embodiment, the chemotherapy agent is dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, the chemotherapy agent is dexamethasone. Dexamethasone has the chemical name (11b, 16a)-9-fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione, and has the structure: 5.4 Methods of use In one embodiment, a method for treating a hematologic malignancy is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib), an inhibitor of the Aurora kinase (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1,UNC1999 or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (by for example, EZM2302), a PLK1 inhibitor (for example, BI2536), a NEK2 inhibitor (for example, JH295), a MEK inhibitor (for example, trametinib), a PHF19 inhibitor, a PIM inhibitor (for example, LGH-447), an IGF-1R inhibitor (for example, linsitinib), an XPO1 inhibitor (for example, selinexor), a BIRC5 inhibitor (for example,YM155) or chemotherapy (for example, bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). Compound A is also provided herein for use in a method of treating a hematologic malignancy, wherein the method comprises administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent provided herein. In one embodiment, a method for preventing a hematologic malignancy is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib), an inhibitor of the Aurora kinase (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1,UNC1999 or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), an inhibitor of CARM1 (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g.,YM155) or chemotherapy (for example, bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). Compound A is also provided herein for use in a method for preventing a hematologic malignancy, wherein the method comprises administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent provided herein. In one embodiment, a method for controlling a hematologic malignancy is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib), an inhibitor of the Aurora kinase (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1,UNC1999 or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (by for example, EZM2302), a PLK1 inhibitor (for example, BI2536), a NEK2 inhibitor (for example, JH295), a MEK inhibitor (for example, trametinib), a PHF19 inhibitor, a PIM inhibitor (for example, LGH-447), an IGF-1R inhibitor (for example, linsitinib), an XPO1 inhibitor (for example, selinexor), a BIRC5 inhibitor (for example,YM155) or chemotherapy (for example, bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). Compound A is also provided herein for use in a method for controlling a hematologic malignancy, wherein the method comprises administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent provided herein. In one realization, hematologic malignancy is leukemia. In one realization, the hematologic malignancy is acute myeloid leukemia. In one realization, acute myeloid leukemia is B-cell acute myeloid leukemia. In one realization, the hematologic malignancy is acute lymphocytic leukemia. In one realization, the hematologic malignancy is chronic lymphocytic leukemia / small lymphocytic lymphoma. In one realization, the hematologic malignancy is myeloma. In one realization, the hematologic malignancy is multiple myeloma. In another realization, multiple myeloma is plasma cell leukemia (PCL). In one realization, the hematologic malignancy is lymphoma. In one realization, the hematologic malignancy is non-Hodgkin lymphoma. In one realization, the hematologic malignancy is diffuse large B-cell lymphoma. In one realization, the hematologic malignancy is T-cell lymphoma. In one realization, the T-cell lymphoma is anaplastic large cell lymphoma (ALCL). In one realization, the T-cell lymphoma is Sézar syndrome. In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization, the hematologic malignancy is marginal zone lymphoma. In one realization, the marginal zone lymphoma is splenic marginal zone lymphoma (SMZL). In one realization, the hematologic malignancy is Hodgkin lymphoma. In one realization, hematologic malignancy is myelodysplastic syndrome. In one embodiment, the LDCBG is an activated B cell-like LDCBG (ABC-LDCBG). In one embodiment, the LDCBG is a germinal center B cell-like LDCBG (GCB-LDCBG). In one embodiment, the LDCBG is an unclassified LDCBG. In one embodiment, the LDCBG is a primary mediastinal B-type LDCBG (LMPCB LDCBG). In one embodiment, the LDCBG is a double-hit LDCBG (DHIT LDCBG), also called cMyc / Bcl-2 mutant LDCBG. In one embodiment, the LDCBG is a triple-hit LDCBG (THIT LDCBG), also called cMyc / Bcl2 / Bcl6 rearranged LDCBG. In one realization, DLBCL is newly diagnosed DLBCL. In one realization, DLBCL is primary DLBCL. In one realization, DLBCL is relapsed DLBCL. In one realization, DLBCL is refractory DLBCL. In one realization, DLBCL is relapsed or refractory DLBCL. In one realization, DLBCL is relapsed / refractory DLBCL. In one realization, DLBCL is refractory to doxorubicin. In one realization, DLBCL is doxorubicin-resistant. In one realization, DLBCL is refractory to one or more of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, bendamustine, lenalidomide, gemcitabine, dexamethasone, ifosfamide, polatuxuab, or CAR-T cell therapy. In one implementation, LDCBG is treated with two or more prior lines of treatment. In one embodiment, DLBCL is a transformed lymphoma. In another embodiment, DLBCL is DLBCL not otherwise specified (NOS). As used herein and unless otherwise specified, "LLC / LLP" or "LLC and / or LLP" means LLC, or LLP, or LLC and LLP. In one embodiment, the methods provided herein are for treating, preventing, or controlling LLC. In one embodiment, the methods provided herein are for treating, preventing, or controlling LLP. In one embodiment, the methods provided herein are for treating, preventing, or controlling both LLC and LLP. In one embodiment, one or more lines of therapy have failed in the subject with CLL / LPP. In one embodiment, at least one prior therapy has failed in the subject. In one embodiment, at least two prior therapies have failed in the subject. In one embodiment, the subject has been previously treated with a Bruton's tyrosine kinase (BTK) inhibitor. In one embodiment, the subject is relapsed or refractory to a BTK inhibitor. In one embodiment, the BTK inhibitor is ibrutinib. In one embodiment, the BTK inhibitor is acalabrutinib. In one embodiment, the BTK inhibitor is zanubrutinib. In one embodiment, the BTK inhibitor is tirabrutinib. In one realization, CLL / LLP is newly diagnosed CLL / LLP. In another realization, CLL / LLP is relapsed or refractory CLL / LLP (R / R CLL / LLP). In one embodiment, CLL is characterized by a mutated IGHV (immunoglobulin heavy chain gene). In another embodiment, CLL is characterized by a non-mutated IGHV. In one embodiment, CLL is characterized by one or more mutations in TP53 (tumor protein 53). In another embodiment, CLL is characterized by wild-type TP53. In one embodiment, CLL is characterized by one or more cytogenetic abnormalities, for example, del(13q), del(11q), del(17p), tri12, t(6;17), del(11q22.3), t(11;14), del(18q), and t(14;19). In one embodiment, CLL is characterized by del(17p). In one realization, CLL is characterized by Richter's transformation (also known as Richter's syndrome). In one scenario, the hematologic malignancy is newly diagnosed. In another scenario, the hematologic malignancy is relapsed or refractory. In one realization, AML is newly diagnosed AML. In one realization, AML is relapsed or refractory AML. In one realization, B-cell AML is newly diagnosed B-cell AML. In one realization, B-cell AML is relapsed or refractory B-cell AML. In one instance, ALL is newly diagnosed ALL. In another instance, ALL is relapsed or refractory ALL. In one realization, MM is newly diagnosed MM. In one realization, MM is refractory relapsed MM. In one realization, LCP is newly diagnosed LCP. In one realization, LCP is relapsed or refractory LCP. In one scenario, LH is newly diagnosed LH. In another scenario, LH is relapsed or refractory LH. In one realization, NHL is newly diagnosed NHL. In another realization, NHL is relapsed or refractory NHL. In one realization, TLC is a newly diagnosed TLC. In one realization, TLC is a relapsed or refractory TLC. In one realization, ALCL is a newly diagnosed ALCL. In one realization, ALCL is a relapsed or refractory ALCL. In one realization, Sézar syndrome is a newly diagnosed Sézar syndrome. In one realization, Sézar syndrome is a relapsed or refractory Sézar syndrome. In one realization, LB is a newly diagnosed LB. In another realization, LB is a relapsed or refractory LB. In one realization, LZM is newly diagnosed LZM. In one realization, LZM is relapsed or refractory LZM. In one realization, LZME is newly diagnosed LZME. In one realization, LZME is relapsed or refractory LZME. In one realization, the SMD is a newly diagnosed SMD. In another realization, the SMD is a relapsed or refractory SMD. In one embodiment, methods are provided herein for achieving a complete response, a partial response, or stable disease in a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib), an Aurora kinase inhibitor (for example,alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447),An IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one embodiment, the hematologic malignancy is NHL. In one embodiment, the hematologic malignancy is DLBCL. In one realization, the hematologic malignancy is TCL (e.g., ALCL or Sézar syndrome). In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization,The hematologic malignancy is HL. In one realization, the hematologic malignancy is LZM (e.g., LZME). In one realization, the hematologic malignancy is MDS. In one embodiment, methods are provided herein for achieving a complete response, a partial response, or stable disease, as determined by the Lugano response criteria in a patient, comprising administering to a patient with DLBCL a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib),an Aurora kinase inhibitor (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor,a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, methods are provided herein for achieving a complete response, a partial response, or stable disease, as determined by the International Workshop on Chronic Lymphocytic Leukemia criteria, in a patient, comprising administering to a patient with CLL / PLL a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib),an Aurora kinase inhibitor (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor,a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, minimal residual disease (MRD) screening can be performed in subjects undergoing bone marrow evaluation to confirm a complete response (CR). In one embodiment, methods are provided herein for achieving minimal residual disease (MRD) negativity in a patient, comprising administering to a patient having CLL / LLP a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat),a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib), an Aurora kinase inhibitor (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin) a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g.,Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one implementation, MRD negativity is measured in peripheral blood and / or bone marrow. In one implementation, MRD negativity lasts for a minimum of 3 months. In one embodiment, methods are provided herein for achieving an increase in overall survival, progression-free survival, event-free survival, time to progression, or disease-free survival in a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib,ruxolitinib, baricitinib, gandotinib, lestaurtinib, or momelotinib), an Aurora kinase inhibitor (e.g., alisertib), an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an inhibitor of LSD-1 (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295),A MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g., linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one realization, the hematologic malignancy is NHL. In one realization, the hematologic malignancy is DLBCL. In one realization, the hematologic malignancy is TCL (e.g.,ALCG or Sézar syndrome. In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization, the hematologic malignancy is HL. In one realization, the hematologic malignancy is MZL (e.g., MZL). In one realization, the hematologic malignancy is MDS. In one embodiment, methods are provided herein for achieving an increase in the overall survival of a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib), an Aurora kinase inhibitor (e.g., alisertib),an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g.,linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one embodiment, the hematologic malignancy is NHL. In one embodiment, the hematologic malignancy is DLBCL. In one embodiment, the hematologic malignancy is TCL (e.g., ALCL or Sézar syndrome). In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization,The hematologic malignancy is HL. In one realization, the hematologic malignancy is LZM (e.g., LZME). In one realization, the hematologic malignancy is MDS. In one embodiment, methods are provided herein for achieving an increase in progression-free survival in a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib), an Aurora kinase inhibitor (for example, alisertib),an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g.,linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one embodiment, the hematologic malignancy is NHL. In one embodiment, the hematologic malignancy is DLBCL. In one realization, the hematologic malignancy is CTL (e.g., ALCL or Sézar syndrome). In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization,The hematologic malignancy is HL. In one realization, the hematologic malignancy is LZM (e.g., LZME). In one realization, the hematologic malignancy is MDS. In one embodiment, methods are provided herein for achieving an increase in event-free survival in a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), or a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, or baricitinib). gandotinib, lestaurtinib or momelotinib), an Aurora kinase inhibitor (for example, alisertib),an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g.,linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one embodiment, the hematologic malignancy is NHL. In one embodiment, the hematologic malignancy is DLBCL. In one embodiment, the hematologic malignancy is TCL (e.g., ALCL or Sézar syndrome). In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization,The hematologic malignancy is HL. In one realization, the hematologic malignancy is LZM (e.g., LZME). In one realization, the hematologic malignancy is MDS. In one embodiment, methods are provided herein for achieving an increase in time to progression in a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib), an Aurora kinase inhibitor (for example, alisertib),an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g.,linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one embodiment, the hematologic malignancy is NHL. In one embodiment, the hematologic malignancy is DLBCL. In one embodiment, the hematologic malignancy is TCL (e.g., ALCL with Sézar syndrome). In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization,The hematologic malignancy is HL. In one realization, the hematologic malignancy is LZM (e.g., LZME). In one realization, the hematologic malignancy is MDS. In one embodiment, methods are provided herein for achieving an increase in disease-free survival in a patient, comprising administering to a patient having a hematologic malignancy provided herein a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is one or more of an HDAC inhibitor (e.g., panobinostat, romidepsin, vorinostat, or cytarinostat), a BCL2 inhibitor (e.g., venetoclax), a BTK inhibitor (e.g., ibrutinib or acalabrutinib), an mTOR inhibitor (e.g., everolimus), a PI3K inhibitor (e.g., idelalisib), a PKCβ inhibitor (e.g., enzastaurin), a SYK inhibitor (e.g., fostamatinib), or a JAK2 inhibitor (e.g., fedratinib, pacritinib, ruxolitinib, or baricitinib). gandotinib, lestaurtinib or momelotinib), an Aurora kinase inhibitor (for example, alisertib),an EZH2 inhibitor (e.g., tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A, EPZ005687, EI1, UNC1999, or sinefungin), a BET inhibitor (e.g., birabresib or Compound B), a hypomethylating agent (e.g., 5-azacitidine or decitabine), a DOT1L inhibitor (e.g., pinometostat), a HAT inhibitor (e.g., C646), a WDR5 inhibitor (e.g., OICR-9429), a DNMT1 inhibitor (e.g., GSK3484862), an LSD-1 inhibitor (e.g., Compound C or seclidemstat), a G9A inhibitor (e.g., UNC 0631), a PRMT5 inhibitor (e.g., GSK3326595), a BRD inhibitor (e.g., LP99), an SUV420H1 / H2 inhibitor (e.g., A-196), a CARM1 inhibitor (e.g., EZM2302), a PLK1 inhibitor (e.g., BI2536), a NEK2 inhibitor (e.g., JH295), a MEK inhibitor (e.g., trametinib), a PHF19 inhibitor, a PIM inhibitor (e.g., LGH-447), an IGF-1R inhibitor (e.g.,linsitinib), an XPO1 inhibitor (e.g., selinexor), a BIRC5 inhibitor (e.g., YM155), or chemotherapy (e.g., bendamustine, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, ifosfamide, melphalan, oxaliplatin, or dexamethasone). In one embodiment, the hematologic malignancy is AML (e.g., B-cell AML). In one embodiment, the hematologic malignancy is ALL. In one embodiment, the hematologic malignancy is CLL / PLL. In one embodiment, the hematologic malignancy is MM. In one embodiment, the hematologic malignancy is CPL. In one embodiment, the hematologic malignancy is NHL. In one embodiment, the hematologic malignancy is DLBCL. In one embodiment, the hematologic malignancy is TCL (e.g., ALCL or Sézar syndrome). In one realization, the hematologic malignancy is Burkitt lymphoma. In one realization,The hematologic malignancy is HL. In one realization, the hematologic malignancy is LZM (e.g., LZME). In one realization, the hematologic malignancy is MDS. In one embodiment, a method provided herein further comprises administering to the patient a therapeutically effective amount of obinutuzumab. In one embodiment, a method is provided herein for treating a hematologic malignancy, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent provided herein (e.g., venetoclax), and further in combination with obinutuzumab. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is panobinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat lactate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is romidepsin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is romidepsin. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vorinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vorinostat. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarinostat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarinostat. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is venetoclax, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is venetoclax. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ibrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ibrutinib. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is everolimus, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is everolimus. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1A, in combination with a second active agent, wherein the second active agent is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is idelalisib. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is enzastaurin.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is an enzastaurin hydrochloride salt. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fostamatinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib disodium hexahydrate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fedratinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fedratinib. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pacritinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pacritinib. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ruxolitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib phosphate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is alisertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is alisertib. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is tazemetostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is tazemetostat. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK126, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK126. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is CPI-1205, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is CPI-1205. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is birabresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is birabresib. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is 5-azacytidine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is 5-azacytidine. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is decitabine. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pinometostat. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is C646, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is C646. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is OICR-9429, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is OICR-9429. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3484862. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound C, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound C.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is the besylate of Compound C. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is seclidemstat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat mesylate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is UNC0631, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is UNC0631. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3326595. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is LP99. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is A-196, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is A-196. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is EZM2302. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is bendamustine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine hydrochloride. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is doxorubicin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin hydrochloride. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is etoposide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide phosphate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is methotrexate, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is methotrexate.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically adequate amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is sodium methotrexate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarabine. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vincristine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine sulfate. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ifosfamide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ifosfamide. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is melphalan, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan.In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan hydrochloride. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is oxaliplatin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is oxaliplatin. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is dexamethasone. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is BI2536, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is BI2536. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is JQ1, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is JQ1. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is rac-CCT 250863, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating DLBCL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is rac-CCT 250863. In one embodiment, a method for treating CLL / LPL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is panobinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat lactate. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is romidepsin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is romidepsin. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vorinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vorinostat. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarinostat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarinostat. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is venetoclax, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is venetoclax. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ibrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ibrutinib. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is everolimus, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is everolimus. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is idelalisib. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is enzastaurin.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is an enzastaurin hydrochloride salt. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fostamatinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib disodium hexahydrate. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fedratinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fedratinib. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pacritinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pacritinib. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ruxolitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib phosphate. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is alisertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is alisertib. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is tazemetostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is tazemetostat. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK126, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK126. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is CPI-1205, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is CPI-1205. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is birabresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is birabresib. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is 5-azacytidine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is 5-azacytidine. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is decitabine. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pinometostat. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is C646, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is C646. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is OICR-9429, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is OICR-9429. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3484862. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound C, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound C.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is the besylate of Compound C. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is seclidemstat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat mesylate. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is UNC0631, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is UNC0631. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3326595. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is LP99. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is A-196, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is A-196. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is EZM2302. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is bendamustine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine hydrochloride. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is doxorubicin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin hydrochloride. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is etoposide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide phosphate. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is methotrexate, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is methotrexate.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is sodium methotrexate. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarabine. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vincristine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine sulfate. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ifosfamide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ifosfamide. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is melphalan, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan.In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan hydrochloride. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is oxaliplatin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is oxaliplatin. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is dexamethasone. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is BI2536, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is BI2536. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is JQ1, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is JQ1. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LLP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is rac-CCT 250863, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating CLL / LPP is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is rac-CCT 250863. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is panobinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat lactate. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is romidepsin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is romidepsin. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vorinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vorinostat. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarinostat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarinostat. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is venetoclax, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is venetoclax. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ibrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ibrutinib. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is everolimus, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is everolimus. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is idelalisib. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is enzastaurin.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is an enzastaurin hydrochloride salt. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fostamatinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib hexahydrate disodium. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fedratinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fedratinib. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pacritinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pacritinib. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ruxolitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib phosphate. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is alisertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is alisertib. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is tazemetostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is tazemetostat. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK126, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK126. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is CPI-1205, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is CPI-1205. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is birabresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is birabresib. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is 5-azacytidine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is 5-azacytidine. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is decitabine. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pinometostat. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is C646, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is C646. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is OICR-9429, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is OICR-9429. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3484862. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound C, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound C.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is the besylate of Compound C. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is seclidemstat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat mesylate. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is UNC0631, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is UNC0631. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3326595. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is LP99. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is A-196, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is A-196. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is EZM2302. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is bendamustine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine hydrochloride. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is doxorubicin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin hydrochloride. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is etoposide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide phosphate. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is methotrexate, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is methotrexate.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is methotrexate sodium. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarabine. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vincristine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine sulfate. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ifosfamide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ifosfamide. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is melphalan, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan.In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan hydrochloride. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is oxaliplatin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is oxaliplatin. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is dexamethasone. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is BI2536, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is BI2536. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is JQ1, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is JQ1. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is rac-CCT 250863, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating AML is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is rac-CCT 250863. In one embodiment, the AML is B-cell AML. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is panobinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat lactate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is romidepsin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is romidepsin. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vorinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vorinostat. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarinostat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarinostat. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is venetoclax, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is venetoclax. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ibrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ibrutinib. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is everolimus, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is everolimus. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is idelalisib. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is enzastaurin.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is an enzastaurin hydrochloride salt. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fostamatinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib disodium hexahydrate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fedratinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fedratinib. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pacritinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pacritinib. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ruxolitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib phosphate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is alisertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is alisertib. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is tazemetostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is tazemetostat. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK126, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK126. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is CPI-1205, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is CPI-1205. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is birabresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is birabresib. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is 5-azacytidine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is 5-azacytidine. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is decitabine. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pinometostat. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is C646, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is C646. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is OICR-9429, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is OICR-9429. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3484862. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound C, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound C.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is the besylate of Compound C. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is seclidemstat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat mesylate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is UNC0631, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is UNC0631. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3326595. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is LP99. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is A-196, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is A-196. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is EZM2302. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is bendamustine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine hydrochloride. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is doxorubicin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin hydrochloride. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is etoposide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide phosphate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is methotrexate, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is methotrexate.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is sodium methotrexate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarabine. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vincristine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine sulfate. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ifosfamide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ifosfamide. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is melphalan, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan.In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan hydrochloride. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is oxaliplatin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is oxaliplatin. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is dexamethasone. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is BI2536, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is BI2536. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is JQ1, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is JQ1. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is rac-CCT 250863, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating ALL is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is rac-CCT 250863. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is panobinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically sufficient amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is panobinostat lactate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is romidepsin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is romidepsin. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vorinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vorinostat. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarinostat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarinostat. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is venetoclax, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is venetoclax. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ibrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ibrutinib. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is everolimus, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is everolimus. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is idelalisib. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is enzastaurin.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is an enzastaurin hydrochloride salt. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fostamatinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fostamatinib disodium hexahydrate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is fedratinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is fedratinib. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pacritinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pacritinib. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ruxolitinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ruxolitinib phosphate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is alisertib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is alisertib. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is tazemetostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is tazemetostat. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK126, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK126. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is CPI-1205, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is CPI-1205. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is birabresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is birabresib. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound B, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound B. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is 5-azacytidine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is 5-azacytidine. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is decitabine. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is pinometostat. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is C646, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is C646. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is OICR-9429, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is OICR-9429. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3484862. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is Compound C, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is Compound C.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is the besylate of Compound C. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is seclidemstat, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is seclidemstat mesylate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is UNC0631, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is UNC0631. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is GSK3326595. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is LP99. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is A-196, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is A-196. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is EZM2302. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is bendamustine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is bendamustine hydrochloride. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is doxorubicin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is doxorubicin hydrochloride. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is etoposide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, a prodrug, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is etoposide phosphate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is methotrexate, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is methotrexate.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is sodium methotrexate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is cytarabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is cytarabine. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is vincristine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is vincristine sulfate. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is ifosfamide, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is ifosfamide. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is melphalan, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan.In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is melphalan hydrochloride. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is oxaliplatin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is oxaliplatin. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is dexamethasone, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is dexamethasone. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is BI2536, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof. In one embodiment, a method for treating MM is provided herein, comprising administering to a patient a therapeutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof (e.g., a hydrochloride salt of Compound 1), in combination with a second active agent, wherein the second active agent is BI2536. In one embodiment, a method for treating multiple myeloma (MM) is provided herein, comprising administering to a patient a therapeutically effective amount of Compound A, in combination with a second active agent, wherein the second active agent is JQ1, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically ac...

Claims

1. A compound for use in a method of treating a hematologic malignancy, wherein the method comprises administering to a patient in need a therapeutically effective amount of the compound in combination with a second active agent, wherein the compound is Compound 1: or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof; and wherein the second active agent is one or more of an EZH2 inhibitor, an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, an SUV420H1 / H2 inhibitor, a CARM1 inhibitor,1. A PLK1 inhibitor, a NEK2 inhibitor, a MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, or a BIRC5 inhibitor.

2. A second active agent for use in a method of treating a hematologic malignancy, wherein the method comprises administering to a patient in need a therapeutically effective amount of a compound in combination with the second active agent, wherein the compound is Compound 1: or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof; and wherein the second active agent is one or more of an EZH2 inhibitor, an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor,a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, an SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, a NEK2 inhibitor, a MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, or a BIRC5 inhibitor.

3. A compound and a second active agent for use in a method of treating a hematologic malignancy, wherein the method comprises administering to a patient in need a therapeutically effective amount of the compound in combination with the second active agent, wherein the compound is Compound 1: or an enantiomer, a mixture of enantiomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof; and wherein the second active agent is one or more of an EZH2 inhibitor, an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor,a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, an SUV420H1 / H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, a NEK2 inhibitor, a MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, or a BIRC5 inhibitor.

4. The compound and / or the second active agent for the use of any of claims 1-3, wherein the second active agent is an EZH2 inhibitor.

5. The compound and / or the second active agent for the use of claim 4, wherein the EZH2 inhibitor is tazemetostat, GSK126, CPI-1205, 3-deazaneplanocin A (DZNep), EPZ005687, El1, UNC1999 or sinefungin, or a stereoisomer,A mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof.

6. The compound and / or second active agent for the use of claim 5, wherein the EZH2 inhibitor is tazemetostat, GSK126, or CPI-1205.

7. The compound and / or second active agent for the use of claim 6, wherein the EZH2 inhibitor is tazemetostat.

8. The compound and / or the second active agent for the use of any of claims 1-3, wherein (a) the second active agent is an HDAC inhibitor, optionally (a)(i) wherein the HDAC inhibitor is panobinostat, romidepsin, or vorinostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof, for example, wherein the HDAC inhibitor is panobinostat, panobinostat lactate, romidepsin, or vorinostat; or (a)(ii) wherein the HDAC inhibitor is an HDAC6 inhibitor, for example,wherein the HDAC6 inhibitor is cytarinostat, or a tautomer, isotopologue or pharmaceutically acceptable salt thereof, optionally wherein the HDAC6 inhibitor is cytarinostat; or (b) the second active agent is a BCL2 inhibitor, optionally wherein the BCL2 inhibitor is venetoclax, or a tautomer, isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the BCL2 inhibitor is venetoclax; or (c) the second active agent is a BTK inhibitor, optionally wherein the BTK inhibitor is ibrutinib, or acalabrutinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the BTK inhibitor is ibrutinib; or (d) the second active agent is an mTOR inhibitor, optionally wherein the mTOR inhibitor is rapamycin or an analogue thereof (also called a rapalog), for example,wherein the mTOR inhibitor is everolimus; or (e) the second active agent is a PI3K inhibitor, optionally wherein the PI3K inhibitor is idelalisib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, for example, wherein the PI3K inhibitor is idelalisib; or (f) the second active agent is a PKCβ inhibitor, optionally wherein the PKCβ inhibitor is enzastaurin, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, for example, wherein the PKCβ inhibitor is enzastaurin or a salt of enzastaurin hydrochloride; or (g) the second active agent is a SYK inhibitor; Optionally, wherein the SYK inhibitor is fostamatinib, or a tautomer, isotopologue, or pharmaceutically acceptable salt thereof, for example,wherein the SYK inhibitor is fostamatinib or fostamatinib disodium hexahydrate; or (h) the second active agent is a JAK2 inhibitor, optionally wherein the JAK2 inhibitor is fedratinib, pacritinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib or momelotinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, for example, wherein the JAK2 inhibitor is fedratinib, pacritinib, ruxolitinib or ruxolitinib phosphate; or (i) the second active agent is an Aurora kinase inhibitor; optionally (i) (i) wherein the Aurora kinase inhibitor is alisertib, or a pharmaceutically acceptable tautomer, isotopologue or salt thereof, for example, wherein the Aurora kinase inhibitor is alisertib; or (ii) wherein the Aurora kinase inhibitor is barasertib, AZD1152-HQPA, danusertib, AT9283, PF-03814735, AMG900, tozasertib, ZM447439, MLN8054, hesperidin, SNS-314,PHA-680632, CYC116, GSK1070916, TAK-901 or CCT137690, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof; or (j) the second active agent is a BET inhibitor, optionally wherein the BET inhibitor is birabresib or 4-[2-(cyclopropylmethoxy)-5-(methanesulfonyl)phenyl]-2-methylisquinoline-1(2H)-one, BMS-986158, RO-6870810, CPI-0610 or molibresib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, e.g. wherein the BET inhibitor is birabresib or 4-[2-(cyclopropylmethoxy)-5-(methanesulfonyl)phenyl1]-2-methylisoquinoline-1(2H)-one; or (k) the second active agent is a hypomethylating agent, optionally wherein the hypomethylating agent is 5-azacytidine or decitabine, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, for example,wherein the hypomethylating agent is 5-azacitidine or decitabine; or (l) the second active agent is a DOT1L inhibitor, optionally wherein the DOT1L inhibitor is SGC0946, or pinometostat, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, for example, wherein the DOT1L inhibitor is pinometostat; or (m) the second active agent is a HAT inhibitor, optionally wherein the HAT inhibitor is C646, or a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof, for example, wherein the HAT inhibitor is C646; or (n) the second active agent is a WDR5 inhibitor, optionally wherein the WDR5 inhibitor is OICR-9429, or a tautomer, isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the WDR5 inhibitor is OICR-9429; or (o) the second active agent is a DNMT1 inhibitor,optionally wherein the DNMT1 inhibitor is a selective DNMT1 inhibitor, for example, wherein the selective DNMT1 inhibitor is GSK3484862, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue, or a pharmaceutically acceptable salt thereof, optionally wherein the selective DNMT1 inhibitor is GSK3484862; or (p) the second active agent is an LSD-1 inhibitor, optionally wherein the LSD-1 inhibitor is 4-(2-(4-aminopiperidin-1-yl)-5-(3-fluoro-4-methoxyphenyl-1)-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-2-fluorobenzonitrile or seclidemstat, or a tautomer, isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the LSD-1 inhibitor is 4-(2-(4-aminopiperidin-1-yl)-5-(3-fluoro-4-methoxyphenyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-2-fluorobenzonitrile, 4-(2-(4-aminopiperidin-1-yl)-5-(3-fluoro-4-methoxyphenyl) besylate -1-methyl-6-oxo-1,6-dihydropyrimidin-4-yl)-2-fluorobenzonitrile,seclidemstat or seclidemstat mesylate; or (q) the second active agent is a G9A inhibitor, optionally wherein the G9A inhibitor is UNC0631, or a tautomer, isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the G9A inhibitor is UNC0631; or (r) the second active agent is a PRMT5 inhibitor, optionally wherein the PRMT5 inhibitor is GSK3326595, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the PRMT5 inhibitor is GSK3326595; or (s) the second active agent is a BRD inhibitor, optionally (s) (i) wherein the BRD inhibitor is a BRD9 / 7 inhibitor, for example, wherein the BRD9 / 7 inhibitor is LP99, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof,optionally wherein the BRD9 / 7 inhibitor is LP99; or (s) (ii) wherein the BRD inhibitor is a BRD4 inhibitor, optionally wherein the BRD4 inhibitor is JQ1; or (t) the second active agent is an SUV420H1 / H2 inhibitor, optionally wherein the SUV420H1 / H2 inhibitor is A-196, or a tautomer, isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the SUV420H1 / H2 inhibitor is A196; or (u) the second active agent is a CARM1 inhibitor, optionally wherein the CARM1 inhibitor is EZM2302, or a stereoisomer, a mixture of stereoisomers, a tautomer, isotopologue or pharmaceutically acceptable salt thereof, for example, wherein the CARM1 inhibitor is EZM2302; or (v) the second agent is a PLK1 inhibitor, optionally wherein the PLK1 inhibitor is BI2536, volasertib, CYC140, onvansertib, GSK461364 or TAK960, or a stereoisomer, a mixture of stereoisomers, an automer,an isotopologue or a pharmaceutically acceptable salt thereof; or (w) the second agent is a NEK2 inhibitor, optionally wherein the NEK2 inhibitor is JH-295 or rac-CCT 250863; or (x) the second agent is a MEK inhibitor, optionally (x)(i) wherein the MEK inhibitor disrupts the function of the RAF / RAS / MEK signal transduction cascade; or (x)(ii) wherein the MEK inhibitor is trametinib, trametinib dimethyl sulfoxide, cobimetinib, binimetinib or selumetinib, or a stereoisomer, a mixture of stereoisomers, a tautomer, an isotopologue or a pharmaceutically acceptable salt thereof; or (y) the second agent is a PHF19 inhibitor; or (z) the second active agent is a PIM inhibitor, optionally wherein the PIM inhibitor is LGH-447, AZD1208, SGI-1776 or TP-3654, or a stereoisomer, a mixture of stereoisomers, a tautomer,an isotopologue or a pharmaceutically acceptable salt thereof; or (aa) the second active agent is an IGF-1R inhibitor, optionally wherein the IGF-1R inhibitor is linsitinib; or (ab) the second active agent is an XPO1 inhibitor, optionally wherein the XPO1 inhibitor is selinexor; or (ac) the second active agent is a BIRC5 inhibitor, optionally wherein the BIRC5 inhibitor is YM155.

9. The compound and / or the second active agent for the use of any of claims 1 to 8, wherein the compound is a hydrochloride salt of Compound 1.

10. The compound and / or the second active agent for the use of any of claims 1 to 9, wherein the hematologic malignancy is acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), multiple myeloma (MM), non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), T-cell lymphoma (TCL), Burkitt lymphoma (BL),Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), marginal zone lymphoma (MZL), or myelodysplastic syndromes (MDS).

11. The compound and / or the second active agent for the use of claim 10, wherein the hematologic malignancy is relapsed or refractory.

12. The compound and / or the second active agent for the use of claim 10, wherein the hematologic malignancy is newly diagnosed.

13. The compound and / or the second active agent for the use of claim 10, wherein the hematologic malignancy is optionally DLBCL. (a) wherein the DLBCL is relapsed or refractory DLBCL, for example, wherein the DLBCL is refractory to one or more of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, bendamustine,lenalidomide or gemcitabine; or (b) wherein the DLBCL is newly diagnosed DLBCL.

14. The compound and / or the second active agent for use according to claim 10, wherein the hematologic malignancy is CLL / PLS, optionally (a) wherein the CLL / PLS is relapsed or refractory CLL / PLS, for example, wherein the CLL / PLS is relapsed or refractory to at least two prior therapies, optionally wherein at least one of the prior therapies is a Bruton's tyrosine kinase (BTK) inhibitor, for example, wherein the BTK inhibitor is ibrutinib, acalabrutinib, zanubrutinib, or tirabrutinib; or (b) wherein the CLL / PLS is newly diagnosed.

15. The compound and / or the second active agent for the use of claim 10, wherein the hematologic malignancy is (a) AML, and the AML is B-cell AML; (b) multiple myeloma, and the multiple myeloma is plasma cell leukemia (PCL); (c) a T-cell lymphoma (TCL),and LCT is an anaplastic large cell lymphoma (ALCL) or Sézar syndrome; or (d) MZL, and MZL is a splenic marginal zone lymphoma (SML).