Alternative Dosing Regimens of Subcutaneous Azacitidine for Myelodysplastic Syndromes

A Multicenter, Randomized, Open-Label Study Comparing Three Alternative Dosing Regimens of Subcutaneous Azacitidine Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes

The purpose of this study is to determine if azacitidine, combined with Best Supportive Care (BSC), is effective in treating myelodysplastic syndromes (MDS) when given according to a different doses and dosing schedules.

Comparison/Control Interventions: The comparison is azacitidine at different doses and schedules.

Duration of Intervention: Treatment lasted for a maximum of 18 cycles, which is up to 24 months.

Inclusion Criteria:

• Diagnosis of refractory anemia, refractory anemia with ringed sideroblasts and at least one of the following: a)Anemia with hemoglobin <110g/L and requires at least 1 unit packed red blood cell transfusions every 28 days; b)Thrombocytopenia with platelet counts <100 x 10^9/L; or c)Neutropenia with absolute neutrophil count <1.5 x 10^9/L.
• OR, Refractory anemia with excess blasts or refractory anemia with excess blast in transformation, according to the French-American-British classification system for MDS.
• At least 18 years of age.
• Have a life expectancy of >7 months.
• Unlikely to proceed to bone marrow or stem cell transplantation therapy following remission.
• Have serum bilirubin levels less than or equal to 1.5 times the upper limit of the normal (ULN) range for the laboratory.
• Have serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels less than or equal to 2 x ULN.
• Have serum creatinine levels less than or equal to 1.5 x ULN.

Exclusion Criteria:

• Secondary MDS.
• Prior treatment with azacitidine.
• Any prior history of Acute Myeloid Leukemia (AML).
• Malignant or metastatic disease within the previous 12 months.
• Uncorrected red cell folate deficiency or vitamin B12 deficiency.
• Hepatic tumors.
• Radiation, chemotherapy, or cytotoxic therapy for non-MDS conditions in the previous 12 months.
• Known or suspected hypersensitivity to azacitidine or mannitol.
• Prior transplantation or cytotoxic therapy to treat MDS. Prior use of Revlimid and Thalomid allowed after 30 day washout.
• Serious medical illness likely to limit survival to less than or equal to 7 months.
• Treatment with androgenic hormones during the previous 14 days
• Active viral infection with known human immunodeficiency virus or vial hepatitis Type B or C.
• Treatment with other investigational drugs with the previous 30 days.