Methods of using (+)-1,4-dihydro-7-[(3s,4s)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid for treatment of antecedent hematologic disorders

Abstract

Methods of treating, preventing or managing antecedent hematologic disorders, such as myelodysplastic syndrome, including chronic myelomonocytic leukemia are disclosed. The methods encompass the administration of SNS-595. Also provided are methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. In certain embodiments, the method of treatment comprise administering SNS-595 in combination with cytarabine. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods are also disclosed.

Description

1. RELATED APPLICATIONS[0001]This application claims priority to U.S. provisional application Ser. No. 61 / 007,229, filed Dec. 10, 2007, entitled “Methods of using (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid for treatment of antecedent hematologic disorders”. The disclosure of the above referenced application is incorporated by reference herein in its entirety.2. FIELD OF THE INVENTION[0002]Provided herein are methods of treating, preventing or managing antecedent hematologic disorders, including myelodysplastic syndrome, with enantiomerically pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, which is also known as SNS-595 or AG-7352.[0003]Further provided is a combination therapy for treatment of antecedent hematologic disorders comprising administering a combination of (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamin...

AI Technical Summary

Benefits of technology

[0024]Provided herein are methods of treating, preventing or managing antecedent hematological disorders, including myelofibrosis, aplastic anemia, paroxysmal nocturnal hemoglobinuria, polycythemia vera, and myelodyspla...

Problems solved by technology

MDS possesses a variable risk of progression to acute leukemia, resulting from ineffective blood cell production.

These drugs are associated with a high incidence of chromosomal abnormalities following exposure and at the time of MDS or acute leukemia diagnosis.

Further, MDS is associated with complications associated with severe cytopenias.

Other complications are development of myelofibrosis, which can accelerate decline in blood counts and increase transfusion requirements.

This type of therapy, however, is both painful for donor and recipient, because of the involvement of invasive procedures and can cause severe and even fatal complications to the recipient, particularly with allogeneic transplant and related Graft Versus Host Disease (GvHD) results.

Therefore, the risk of GvHD restricts the use of bone marrow transplantation to patients with otherwise fatal diseases.

Further, as most patients are elderly and only a few young MDS patients will have a matched donor, the use of bone marrow transplantation is limited.

Unfortunately, hematopoietic growth factors have not proven effective in many clinical settings.

Clinical trials of MDS patients treated with recombinant human GM-CSF and G-CSF have shown that while these cytokines can restore granulocytopoiesis in treated patients, their efficacy is restricted to the granulocyte or monocyte lineage with little or no improvement in hemoglobin or platelet counts.

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