Venetoclax Combined With Azacitidine for Consolidation Therapy in AML

Soochow University

Status and phase: Not yet enrolling; Phase 2

Conditions: Venentoclax; Consolidation Therapy; Hematopoietic Stem Cell Transplant (HSCT); High Risk; Acute Myeloid Leukemia

Treatments: Drug: Ara-C Group; Drug: VEN/AZA condsolidation

Study type: Interventional

Funder types: Other

Identifiers

NCT07425782

SCH-AML-VenAza-C

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 216 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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216 participants in 2 patient groups

Ara-C Consolidation Arm

Active Comparator group

Description:

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).

Treatment:

Drug: Ara-C Group

VA Consolidation Chemotherapy Arm

Experimental group

Description:

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.

Treatment:

Drug: VEN/AZA condsolidation