A Prospective, Randomized, Open-Label Study of Venetoclax Combined With Azacitidine for Consolidation Therapy in Adult Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Leukemia free survival
研究概览
简要总结
The goal of this clinical trial is to compare the efficacy and safety of a venetoclax-based consolidation therapy versus conventional consolidation chemotherapy in newly diagnosed adult patients with high-risk acute myeloid leukemia (AML) who have achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) after induction therapy with venetoclax and azacitidine and are planned for transplantation.
The main questions it aims to answer are:
Does consolidation therapy with a venetoclax-containing regimen lead to superior clinical outcomes compared to conventional chemotherapy in this specific patient population? What is the comparative safety profile of the venetoclax-containing consolidation regimen versus conventional chemotherapy in these patients? Participants will be randomly assigned to receive either the venetoclax-based consolidation therapy or the conventional consolidation chemotherapy before undergoing transplantation.
详细描述
Background and Rationale:Current AML frontline therapy is shifting from intensive chemotherapy toward precision-based approaches. Venetoclax combined with hypomethylating agents (e.g., azacitidine) has become the standard of care for older or chemotherapy-ineligible patients and has shown comparable efficacy and improved safety in younger, fit patients compared with intensive chemotherapy.Pre-transplant consolidation remains a critical phase for reducing relapse risk; however, conventional cytarabine-based regimens are associated with high relapse rates. To date, no prospective studies have investigated venetoclax-based consolidation in AML. This trial aims to address this gap and provide evidence to guide post-remission therapy.
Study Design and Interventions:Eligible patients (aged ≥18 years) with newly diagnosed high-risk AML who achieved CR/CRi after 1-2 cycles of venetoclax plus azacitidine induction will be randomized 1:1 to:Experimental arm: Venetoclax-based consolidation regimen (per protocol)；Comparator arm: Conventional intermediate-dose cytarabine consolidation (per protocol).All patients will proceed to allo-HSCT after 1-2 consolidation cycles.
Endpoints:Primary: Leukemia-free survival (LFS). Key Secondary: MRD-negative rate before transplantation, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and safety profile.
Significance:This study will provide high-level evidence to guide consolidation strategies for high-risk AML in the venetoclax era, with the goal of improving transplant outcomes and long-term survival.
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 AML confirmed by bone marrow morphology, flow cytometry, and molecular genetics, meeting WHO 2022 classification criteria;
- •Age ≥ 18 years;
- •Classified as high-risk according to the European LeukemiaNet (ELN) prognostic risk stratification for AML, including AML with myelodysplasia-related changes (AML-MRC) and therapy-related acute myeloid leukemia (t-AML);
- •Achieved CR or CRi after ≤ 2 cycles of VA induction chemotherapy;
- •Availability of a suitable donor, with plans to undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT);
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
- •Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN), total bilirubin ≤ 2 times ULN; left ventricular ejection fraction (LVEF) ≥ 50% as shown by echocardiography (ECHO); expected survival > 8 weeks;
- •Voluntarily signed the informed consent form and can understand and comply with study requirements.
排除标准
- •Presence of clinically active cardiovascular disease, such as uncontrolled ventricular arrhythmia, uncontrolled hypertension, congestive heart failure, cardiac disease classified as Class 3 or 4 according to the New York Heart Association (NYHA) Functional Classification, or a history of myocardial infarction within 3 months prior to screening;
- •Active central nervous system leukemia (CNSL) or extramedullary infiltration of leukemia;
- •Other serious diseases that may limit the patient's participation in this trial (e.g., severe infection, renal failure);
- •Known human immunodeficiency virus (HIV) infection or uncontrolled severe viral hepatitis;
- •Pregnant or breastfeeding women;
- •Inability to understand, comply with the study protocol, or sign the informed consent form;
- •Any other conditions deemed by the investigator as unsuitable for participation in this study.
研究组 & 干预措施
Ara-C Consolidation Arm
AraC (Cytarabine) 1-2 g/m², administered intravenously every 12 hours on days 1-3, may be combined with anthracycline/anthraquinone agents. After completing 1-2 cycles of consolidation therapy, the patient proceeds to allogeneic hematopoietic stem cell transplantation (allo-HSCT).
干预措施: Ara-C Group (Drug)
VA Consolidation Chemotherapy Arm
VEN: 400 mg, orally, days 1-28 (Venetoclax dosage must be adjusted per prescribing information/guidelines based on concomitant use of CYP3A4 inhibitors); AZA: 75 mg/m²/day, subcutaneously, days 1-7; Proceed to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after completing 1-2 cycles of consolidation therapy.
干预措施: VEN/AZA condsolidation (Drug)
结局指标
主要结局
Leukemia free survival
时间窗: From date of complete remission until the date of first documented relapse or date of death from any cause, whichever came first, assessed up to 2 years.
Time from date of achieving complete remission until date of first documented hematologic relapse, extramedullary relapse, or death from any cause, whichever occurs first.
次要结局
- Pretransplantation MRD negative rate(From the end of the last consolidation therapy to the initiation of conditioning regimen for allogeneic hematopoietic stem cell transplantation, within approximately 1 month.)
- Overall survival(From the first day of randomization to the date of death, assesed up to 2 years.)
- Cumulative relapse rate(From date of achieving remission to the date of death from any cause, assessed up to 2 years.)
- Non-relapse mortality(From date of randomization until date of death without prior relapse or disease progression, assessed up to 2 years.)
研究者
CHEN Jia
Chief Physician of Hematology. Clinical Professor. Principal Investigator
The First Affiliated Hospital of Soochow University