A Randomized, Multicenter, Phase II Study of Maintenance Azacitidine and Venetoclax Versus an Allogeneic Stem Cell Transplant in Older Patients (65 Years and Older) With Acute Myeloid Leukemia Who Achieve an MRD Negative Complete Remission After Induction With Azacitidine and Venetoclax
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 100
- 试验地点
- 7
- 主要终点
- 1-year Relapse free survival (RFS)
研究概览
简要总结
The researchers are doing this study to find out if an allogeneic hematopoietic stem cell transplant (HSCT) or maintenance therapy with azacitidine and venetoclax is more effective at keeping AML from coming back (relapsing).
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients ≥65 years of age at the time of signing the informed consent form.
- •Confirmed diagnosis of acute myeloid leukemia according to the ELN 2017 criteria
- •Treatment with azacitidine and venetoclax for the diagnosis of AML
- •o The first cycle of study treatment will start 28-42 days after the start of the second cycle of SOC AZA/VEN. In the event that patients can't be admitted for allo-HCT until after Day 42 due to donor related issues, an additional cycle of AZA/VEN will be allowed as a bridge to the transplant, and then initiation of conditioning will start no later than day 42 after the start of the third cycle.
- •Patients with adequate organ function to be considered as candidates for allo-HCT:
- •Cardiac: asymptomatic or if symptomatic, then LVEF at rest must be >40% and must improve with exercise.
- •Renal: CrCl ≥50 ml/min (measured or calculated/estimated).
- •Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
- •Hepatic: < 5x ULN liver function tests and < 2x ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
- •KPS of ≥ 70
- •Patients with suitable donor for allo-HCT
- •Patients must achieve a morphologic remission <5% blast with MRD negative status by flow cytometry (defined as one or less residual leukemic blasts per 1000 leukocytes (or 10^3)) meeting one of the below:
- •Complete remission (CR) defined as: <5% blasts with ANC> 1000 AND Plt >100K
- •CRh defined as <5% blasts with ANC > 500 AND Plt >50K
- •CRi defined as <5% blasts with ANC< 1000 OR Plt < 100K
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
排除标准
- •Patients who are not considered to be transplant eligible (either due to lack of suitable donor or due to comorbidities/performance status). The reason the patient is not considered transplant eligible will be documented in the eCRF.
- •History of prior allo-HCT
- •Patients who underwent prior leukemia directed treatment (other than aza/ven)
- •Patients with CNS involvement at any time point prior to enrollment.
- •Patients with previous exposure to venetoclax or an HMA for the treatment of a myeloid malignancy
- •Patients who are planned for treatment other than AZA/VEN
- •Patients who are planned for treatment with HMA/VEN with another agent (e.g. a "triplet")
- •Presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.
研究组 & 干预措施
Allogeneic hematopoietic stem cell transplantation (Allo-HCT arm)
Patients who are randomized to the transplant arm will start the conditioning regimen no later than 6 weeks (day 42) after C2D1 of AZA/VEN.
干预措施: Allogeneic hematopoietic stem cell transplantation (Procedure)
maintenance arm Azacitidine and Venetoclax (AZA/VEN)
Patients randomized to the maintenance arm (AZA/VEN) will be treated with azacitidine given daily for 7 days starting on Day 1 of each Cycle (7 consecutive days or a total of 7 days with a 2 day break due to weekends or holidays is permissible). Venetoclax will be taken orally daily for 28 days. A cycle will be considered 28 days.
干预措施: Azacitidine (AZA) (Drug)
maintenance arm Azacitidine and Venetoclax (AZA/VEN)
Patients randomized to the maintenance arm (AZA/VEN) will be treated with azacitidine given daily for 7 days starting on Day 1 of each Cycle (7 consecutive days or a total of 7 days with a 2 day break due to weekends or holidays is permissible). Venetoclax will be taken orally daily for 28 days. A cycle will be considered 28 days.
干预措施: Venetoclax (Drug)
结局指标
主要结局
1-year Relapse free survival (RFS)
时间窗: 1 year
Relapse free survival (RFS)- will be defined with patients being alive and without any evidence of disease. i.e. no morphologic relapse and no emergence of minimal residual disease. In the event of emergence of MRD without a morphologic relapse, this will be defined as relapse only if documented on 2 separate time points. For patients alive and in remission at the data cut-off, RFS will be censored at the last assessment date.
次要结局
- Overall survival (OS)(3 years)