Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)

A Phase 4, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes.

The primary purpose of this study is to determine the effectiveness and safety of azacitidine in the treatment of Taiwanese subjects with higher-risk Myelodysplastic Syndrome (MDS).

The study has 3 phases which include the Screening Phase, the Treatment Phase, and the Post-Treatment Phase and outlined as follows:

Screening Phase:

Subjects will provide informed consent prior to undergoing any study-related procedures. Screening procedures are to take place within 28 days prior to the initiation of azacitidine treatment (Day 1, Cycle 1). Subject eligibility will be based on central pathology review. Bone marrow aspirate and bone marrow biopsy will be collected at screening and sent for morphological assessment by a central pathology reviewer prior to the subject receiving IP. The central pathology reviewer will document the MDS classification according to the FAB and WHO criteria (Appendix A and B, respectively).

A standard cytogenetic metaphase preparation will be prepared from the bone marrow aspirate and sent to the local or central laboratory (for sites without local analysis capability) for the cytogenetic analysis prior to receiving IP.

The IPSS score will be calculated using the central reviewer's pathology report for bone marrow blast percentage, local cytogenetic assessment for karyotype, and central laboratory report for number of cytopenias (Appendix D).

Treatment Phase:

The first dose of azacitidine for each subject begins on Day 1 of Cycle 1. All subjects will receive azacitidine 75 mg/m2/day SC for 7 days every 28 days for up to 6 cycles, unless they are discontinued from treatment. Visits during the treatment phase are to be scheduled weekly for the first 2 cycles, then every other week for all subsequent cycles throughout the rest of the study. Safety and efficacy measures are to be performed weekly, every other week, every 4 weeks, or at 24 weeks, depending on the procedure.

Post-Treatment Phase:

All discontinued subjects, regardless of reason for discontinuation, should undergo end-of-study procedures at the time of study discontinuation. Subjects will have a follow-up visit for the collection of adverse events up to 28 days after last IP dose.

Inclusion Criteria:

• A diagnosis of RAEB or RAEB-T according to FAB classification for MDS and with an IPSS score of intermediate-2 or high risk or a diagnosis of myelodysplastic CMML per modified FAB criteria.
• Taiwanese males and females ≥ 18 years of age
• ECOG 0, 1, or 2;
• Adequate hepatic and renal organ function

Exclusion Criteria:

• Previous treatment with azacitidine or decitabine
• Malignant disease diagnosed within prior 12 months
• Uncorrected red cell folate deficiency or vitamin B12 deficiency
• Diagnosis of metastatic disease
• Malignant hepatic tumors
• Known or suspected hypersensitivity to azacitidine or mannitol
• Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS
• Treatment with erythropoietin or myeloid growth factors during the 21 days prior to Day 1 of Cycle 1 or androgenic hormones during the 14 days prior to Day 1 of Cycle 1;
• Active HIV or viral hepatitis type B or C
• Treatment with other investigational drugs within the previous 30 days prior to Day 1 of Cycle 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period;
• Pregnant or lactating females