A Multicenter, Randomized, Open-Label Study Comparing Three Alternative Dosing Regimens of Subcutaneous Azacitidine Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 151
- 试验地点
- 30
- 主要终点
- Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •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.
排除标准
- •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.
研究组 & 干预措施
Aza-5
Azacitidine administered subcutaneously at 75mg/m^2 for 5 days on a 28 day cycle.
干预措施: azacitidine (Drug)
Aza-5-2-2
Azacitidine administered subcutaneously at 75mg/m^2 for 5days with 2 days off, then for an additional 2 days, on a 28 day cycle.
干预措施: azacitidine (Drug)
Aza-5-2-5
Azacitidine administered subcutaneously at 50mg/m^2 for 5 days with 2 days off, then for an additional 5 days, on a 28 day cycle.
干预措施: azacitidine (Drug)
Maintenance Aza 5 days q 4 weeks
Azacitidine administered subcutaneously at 75mg/m^2 for 5 days every 4 weeks.
干预措施: azacitidine (Drug)
Maintenance Aza 5 days q 6 weeks
Azacitidine administered subcutaneously at 75mg/m^2 for 5 days every 6 weeks.
干预措施: azacitidine (Drug)
结局指标
主要结局
Number of Participants In Best Hematological Response Categories as Determined by the Investigator Using International Working Group 2000 (IWG 2000) Criteria For Myelodysplastic Syndromes (MDS) During the Initial Study Period.
时间窗: Day 1 (randomization) to 6 months
Participant counts by best hematological response; complete remission(CR) is better than a partial remission(PR) which is better than stable disease(SD). Investigator determined responses followed IWG 2000 criteria for MDS CR: repeat bone marrow show \<5% myeloblasts, and peripheral blood evaluations lasting \>=2 months of hemoglobin(\>110 g/L), neutrophils(\>=1.5x10\^9/L), platelets(\>=100x10\^9/L), blasts (0%) and no dysplasia PR is the same as CR for peripheral blood: bone marrow shows blasts decrease by \>=50% or a less advanced FAB classification from pretreatment (see Population Descrip)
Number of Participants With Overall Best Hematologic Response and Hematologic Improvement Based on IWG 2000 Criteria For MDS During the Initial Study Period
时间窗: Day 1 (randomization) to 6 months
Number of participants whose best hematological outcome was either complete remission (CR), partial remission (PR) (as determined by the investigator), or any hematologic improvement (based on the IWG 2000 criteria for MDS). See previous outcomes for detailed definitions.
Number of Participants With Best Hematological Improvement Derived Using International Working Group 2000 (IWG 2000) Criteria for MDS During the Initial Study Period.
时间窗: Day 1 (randomization) to 6 months
IWG 2000 Criteria: Pretreatment=hemoglobin \<110g/L or RBC transfusion-dependence, platelet count \<100x10\^9/L or platelet transfusion dependence, absolute neutrophil count \<1.5x10\^9/L. Erythroid response: Major-\>20g/L increase in hemoglobin or transfusion independence. Minor- 10-20g/L increase in hemoglobin or \>=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of platelet count by \>=30x10\^9/L or platelet transfusion independence. Minor-\>=50% increase in platelet count with net increase \>10x10\^9/L but \<30x10\^9/L. (continued in Population Description)
Number of Participants Who Improved or Maintained The Hematologic Response From the Initial Study Period (Based on IWG 2000 Criteria For MDS) During the Maintenance Period
时间窗: 24 months
Hematologic response during the maintenance period are compared to the response in the initial study period. Initial response could have been a complete remission, a partial remission, stable disease or a hematologic improvement. Maintenance period best response is after randomization to a maintenance arm for those randomized, and is after the start of cycle 7 for those remaining on initial period treatment throughout the study.
次要结局
- Change From Baseline in Absolute Neutrophil Count (ANC) at the End of the Maintenance Study Period (Month 24)(24 months)
- Red Blood Cell (RBC) Transfusion Status at Baseline and End of Initial Study Period (6 Months)(6 months)
- Change From Baseline in Platelets at the End of Initial Study Period (6 Months)(6 months)
- Change From Baseline in Absolute Neutrophil Count (ANC) at the End of Initial Study Period (6 Months)(6 months)
- Platelet Transfusion Status at Baseline and End of Initial Study Period (6 Months)(6 months)
- Baseline Hemoglobin Values(Day 1 (randomization))
- Change From Baseline in Hemoglobin at End of Initial Study Period (6 Months)(6 months)
- Change From Baseline in Hemoglobin at the End of the Maintenance Study Period(24 months)
- Baseline Platelet Values(Day 1 (randomization))
- Platelet Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)(24 months)
- Red Blood Cell (RBC) Transfusion Status at Baseline and End of Maintenance Study Period (24 Months)(24 months)
- Change From Baseline in Platelets at the End of the Maintenance Study Period (Month 24)(24 months)
- Baseline Absolute Neutrophil Count (ANC) Values(Day 1 (randomization))
- Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Initial Study Period(6 months)
- Change From Baseline in the Number of Infections Requiring Treatment With IV Antibiotics Per Treatment Cycle (28 Days) for the Maintenance Study Period(24 months)