A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia in Complete Remission
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 472
- 试验地点
- 223
- 主要终点
- Kaplan-Meier (K-M) Estimate for Overall Survival (OS)
研究概览
简要总结
This study enrolled 472 participants, aged 55 or older, with a diagnosis of de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or chronic myelomonocytic leukemia (CMML), and who have achieved first complete remission (CR)/ complete remission with incomplete blood count recovery (CRi) following induction with or without consolidation chemotherapy.
The study is amended to include an extension phase (EP). The EP allows participants who are currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed by the investigator, to continue receiving oral azacitidine after unblinding by sponsor until the participant meets the criteria for study discontinuation or until oral azacitidine becomes commercially available and reimbursed. In addition, all participants in the placebo arm and participants who had been discontinued from the treatment phase (irrespective of randomization arm) and continuing in the follow-up phase will be followed for survival in the EP.
详细描述
This is an international, multicenter, placebo-controlled, Phase 3 study with a double-blind, randomized, parallel-group design in subjects with de novo AML or AML secondary to prior diagnosis of myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) aged ≥ 55 years, who are in first CR/CRi following induction therapy with or without consolidation chemotherapy. The study consists of 3 phases; the pre-randomization phase (screening phase), the treatment phase, and the follow-up phase.
The study is amended to include an extension phase (EP). The EP allows participants who are currently receiving oral azacitidine and who are demonstrating clinical benefit as assessed by the Investigator, to continue receiving oral azacitidine after unblinding by sponsor until they meet the criteria for study discontinuation or until oral azacitidine becomes commercially available and reimbursed. In addition, all participants in the placebo arm and participants who had been discontinued from the treatment phase (irrespective of randomization arm) and continuing in the follow-up phase will be followed for survival in the EP.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants ≥ 55 years of age
- •Newly diagnosed, histologically confirmed de novo acute myeloid leukemia (AML) or AML secondary to prior myelodysplastic disease or CMML (Chronic myelomonocytic leukemia)
- •First complete remission (CR)/ complete remission with incomplete blood count recovery (CRi) with induction therapy with intensive chemotherapy with or without consolidation therapy within 4 months (+/- 7 days of achieving CR or CRi)
- •Eastern Cooperative Oncology Group (ECOG) performance status - 0, 1, 2, 3
- •Key Inclusion Criteria in the Extended Phase of the study:
- •At the Investigator's discretion and with approval of the sponsor, participants meeting all of the following eligibility criteria are eligible to enter the extension phase:
- •All participants randomized into the oral azacitidine or placebo arm and are continuing in either the treatment phase or follow-up phase of the CC-486-AML-001 study;
- •Participants randomized to oral azacitidine treatment arm and continuing in the treatment phase demonstrating clinical benefit as assessed by the investigator are eligible to receive oral azacitidine in the extension phase (EP);
- •Participants randomized into placebo arm of the study will not receive oral azacitidine in the EP, but will be followed for survival in the EP;
- •Participants currently in the follow-up phase will continue to be followed for survival in the EP;
- •Participants who have signed the informed consent for the EP of the study;
- •Participants who do not meet any of the criteria for study discontinuation
排除标准
- •AML with inversion (inv)(16), translocation = t(8;21), t(16;16), t(15;17), or t(9;22) or molecular evidence of such translocations
- •Prior bone marrow or stem cell transplantation
- •Have achieved CR/CRi following therapy with hypomethylating agents
- •Diagnosis of malignant disease within the previous 12 months
- •Proven central nervous system (CNS) leukemia
研究组 & 干预措施
Oral Azacitidine
300 mg oral azacitidine on days 1 to 14 of each 28-day treatment cycle.
干预措施: Oral Azacitidine (Drug)
Placebo
Identically matching placebo tablets on days 1 to 14 of each 28-day treatment cycle.
干预措施: Placebo (Drug)
结局指标
主要结局
Kaplan-Meier (K-M) Estimate for Overall Survival (OS)
时间窗: Day 1 (randomization) up to data cut off date of 15 July 2019; median follow-up for OS estimated by the reverse K-M method was 41.2 months for all participants.
Overall survival was defined as time from randomization to death from any cause; participants surviving at the end of the follow-up period, or who withdraw consent, or who were lost to follow up were censored at the date last known alive.
次要结局
- Kaplan-Meier Estimate of Relapse Free Survival (RFS)(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Kaplan-Meier Estimate of Time to Relapse(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Kaplan-Meier Estimates of Time to Discontinuation From Treatment(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score From Baseline(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score From Baseline(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale(From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months)
- Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)
- Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year(From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months)