A Prospective, Randomized, Open-Label Study of Venetoclax Combined With Azacitidine for Consolidation Therapy in Adult Intermediate-Risk Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 226
- 试验地点
- 1
- 主要终点
- Leukemia-Free Survival (LFS)
研究概览
简要总结
This clinical trial aims to compare the efficacy and safety of venetoclax-based consolidation therapy versus conventional consolidation chemotherapy (intermediate/high-dose cytarabine) in newly diagnosed adult patients with intermediate-risk acute myeloid leukemia (AML). Participants must have achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) after induction therapy with venetoclax and azacitidine and are planned to undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT).
详细描述
The goal of this prospective, randomized, open-label, multi-center study is to demonstrate that consolidation therapy with venetoclax + azacitidine (VA) is non-inferior to conventional intensive chemotherapy (cytarabine-based regimens) in this specific patient population, while offering a more favorable safety profile.Eligible patients will be randomized 1:1 to receive either 1-2 cycles of VA (Venetoclax 400mg d1-28 + Azacitidine 75mg/m² d1-7) or 1-2 cycles of intermediate/high-dose cytarabine (AraC) ± anthracycline. The primary endpoint is 2-year Leukemia-Free Survival (LFS). Secondary endpoints include pre-transplant MRD-negative rate, Overall Survival (OS), Cumulative Incidence of Relapse (CIR), Non-Relapse Mortality (NRM), and safety profile (CTCAE v5.0). This study will provide high-level evidence for consolidation therapy in intermediate-risk AML in the venetoclax era.
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
- •Confirmed diagnosis of acute myeloid leukemia (AML) according to WHO 2022 classification criteria;
- •Age ≥ 18 years;
- •Classified as intermediate-risk based on European LeukemiaNet (ELN) 2022 prognostic risk stratification;
- •Achieved first complete remission (CR) or CR with incomplete hematologic recovery (CRi) after ≤ 2 cycles of Venetoclax + Azacitidine (VA) induction therapy;
- •Has a suitable donor and is planned to undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT);
- •ECOG performance status score 0 to 2
- •Adequate organ function: creatinine clearance ≥ 50 mL/min; AST and ALT ≤ 3 × ULN; total bilirubin ≤ 2 × ULN; LVEF ≥ 50%; life expectancy > 8 weeks
- •Voluntarily signed informed consent form and able to comply with study requirements
排除标准
- •Clinically active cardiovascular disease (uncontrolled arrhythmia/hypertension, NYHA Class 3/4 heart failure, myocardial infarction within 3 months)
- •Active central nervous system (CNS) leukemia or extramedullary infiltration
- •Other serious diseases limiting participation (e.g., severe infection, renal failure)
- •Known HIV infection or uncontrolled severe viral hepatitis
- •Pregnant or breastfeeding women
- •Inability to understand, comply with protocol, or sign informed consent
- •Any other conditions deemed unsuitable by the investigator
研究组 & 干预措施
Venetoclax + Azacitidine Consolidation
Venetoclax: 400 mg, orally, once daily on Days 1-28. (Dose adjustment required per prescribing information/guidelines when combined with CYP3A4 inhibitors).
Azacitidine: 75 mg/m²/day, subcutaneously or intravenously, on Days 1-7. Patients will receive 1-2 cycles of this regimen before proceeding to allo-HSCT.
干预措施: Venetoclax and Azacitidine (Drug)
Conventional Consolidation Chemotherapy
Cytarabine (AraC): ≥6g/m² per cycle (e.g., 1-2g/m², every 12 hours on days 1-3), administered intravenously.
May be combined with anthracycline/anthraquinone agents per standard practice. Patients will receive 1-2 cycles of this regimen before proceeding to allo-HSCT.
干预措施: Cytarabine ± Anthracycline (Drug)
结局指标
主要结局
Leukemia-Free Survival (LFS)
时间窗: From the date of randomization to the date of first documented hematologic relapse, extramedullary relapse, or death from any cause, assessed up to 2 years.
Time from randomization to the first occurrence of relapse or death, whichever comes first.
次要结局
- Pretransplantation MRD-Negative Rate(From the end of the last consolidation therapy to the initiation of conditioning regimen for allo-HSCT, approximately within 1 month.)
- Overall Survival (OS)(From the first day of randomization to the date of death from any cause, assessed up to 2 years.)
- Cumulative Incidence of Relapse (CIR)(From the date of randomization to the date of hematologic relapse, assessed up to 2 years.)
- Non-Relapse Mortality (NRM)(From the date of randomization until the date of death without prior relapse or disease progression, assessed up to 2 years.)
- Incidence of Adverse Events (Safety Profile)(Throughout the consolidation treatment period and up to 30 days post-treatment.)
研究者
CHEN Jia
Chief Physician，Associate Professor
The First Affiliated Hospital of Soochow University