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.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 44
- 试验地点
- 11
- 主要终点
- Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator
研究概览
简要总结
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).
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Single-Arm
Azacitidine 75 mg/m^2/day Subcutaneous for 7 days Day every 28 days for up to 6 cycles
干预措施: Azacitidine (Drug)
结局指标
主要结局
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator
时间窗: Response assessed at end of cycle 6; through week 24; End of study
Hematologic Response according to the 2000 International Working Group (IWG) response criteria for MDS was based on the Investigators determination and defined as: * Complete Response (CR): repeat bone marrow (BM) shows \<5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (\>110 g/L), neutrophils (≥1.5x10\^9/L), platelets (≥100x10\^9/L), blasts (0%) and no dysplasia * Partial Response (PR): same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment * Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months. * Failure: death during treatment or disease progression * Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence * Disease Progression: change in blast levels * Disease Transformation to AML
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor
时间窗: Response assessed at end of cycle 6; through week 24; End of study
Hematologic improvements (HI) have 4 categories: 1. Erythroid response (HI-E): Major \>20g/L increase or transfusion independent. Minor- 10-20g/L increase or ≥50% decrease in transfusion requirements. 2. Platelet response (HI-P): Major absolute increase of ≥30x10\^9/L or platelet transfusion independence. Minor-≥50% increase. 3. Neutrophil response (HI-N): Major 100% increase or an absolute increase of \>0.5x10\^9/L. Minor-≥100% increase and absolute increase of \<0.5x10\^9/L 4. Progression or relapse after HI Overall hematological improvement (HI) was defined as any type (major or minor) of improvement of HI-E, HI-P, or HI-N. Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Sponsor's determination was derived using clinically relevant data. Denominator for progression/relapse after HI included participants who had achieved HI.
次要结局
- Number of Red Blood Cell (RBC) Transfusions by Cycle(Up to week 24;The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.)
- Number of Platelet Transfusions by Cycle(Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.)
- Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days(Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.)
- Number of Participants With Adverse Events (AE)(From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days))
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine(Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)
- Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine(Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)
- Maximum Observed Plasma Concentration (Cmax) of Azacitidine(Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)
- Time to Maximum Plasma Concentration (Tmax) of Azacitidine(Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)
- Terminal Phase of Half-life (T1/2) of Azacitidine(Timeframe: Day 7 pre-dose at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)
- Apparent Total Plasma Clearance (CL/F) of Azacitidine(Timeframe: Days 5 and 6 at predose and Day 7 (pre-dose) at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)
- Apparent Volume of Distribution (Vd/F) of Azacitidine(Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose)