Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)
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).
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- Proportion of participants with a hematologic response (defined as Complete Response and Partial Response), and Hematologic Improvement based on International Working Group 2000 response criteria for Myelodysplastic Syndromes. [ Time Frame: 7 months ] [ Designated as safety issue: No ]Proportion of participants with a hematologic response (defined as Complete Response and Partial Response), and Hematologic Improvement based on International Working Group 2000 response criteria for Myelodysplastic Syndromes.
- Number of red blood cell transfusions [ Time Frame: 7 months ] [ Designated as safety issue: No ]
- Number of platelet transfusions [ Time Frame: 7 months ] [ Designated as safety issue: No ]
- Number of infections requiring intravenous antibiotics [ Time Frame: 7 months ] [ Designated as safety issue: No ]
- Safety (type, frequency, severity, and relationship of adverse events to azacitidine) [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
- Steady-state plasma azacitidine concentrations [ Time Frame: 7 days ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Estimated Study Completion Date:||September 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Azacitidine 75 mg/m^2/day Subcutaneous for 7 days Day every 28 days for up to 6 cycles
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 the treatment. In addition, subjects may receive best supportive care as needed, including antibiotics and transfusions, per Investigator discretion.
The study has 3 phases which include the Screening Phase, the Treatment Phase, and the Post-Treatment Phase and outlined as follows:
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).
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.
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.
|Changhua Christian Hospital|
|Changhua, Taiwan, 500|
|Chiayi Chang Gung Memorial Hospital|
|Chiayi, Taiwan, 613|
|Buddhist Tzu Chi General Hospital-Hualien Tzu Chi Medical Center|
|Hualien, Taiwan, 970|
|Kaohsiung Medical Hospital University|
|Kaohsiung, Taiwan, 807|
|Kaohsiung Chang Gung Memorial Hospital|
|Kaohsiung City, Taiwan, 833|
|New Taipei City, Taiwan, 23561|
|China Medical University Hospital|
|Taichung, Taiwan, 404|
|National Cheng Kung University Hospital|
|Tainan, Taiwan, 704|
|National Taiwan University Hospital|
|Taipei, Taiwan, 10002|
|Taipei Veterans General Hospital|
|Taipei, Taiwan, 11217|
|Tri-Service General Hospital|
|Taipei, Taiwan, 11490|
|Study Director:||C L Beach, PharmD||Celgene Corporation|