VA Consolidation in Intermediate-Risk AML

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.

• Venetoclax and Azacitidine (Drug): 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.
• Cytarabine ± Anthracycline (Drug): 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.

Primary outcomes

• Leukemia-Free Survival (LFS) [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.

Secondary outcomes

• 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.]: Proportion of patients who achieve minimal residual disease (MRD) negativity prior to hematopoietic stem cell transplantation, as assessed by multi-parameter flow cytometry.
• 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.]: Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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