Comparison of VA and D/IA Induction Regimens in Elderly Fit Acute Myeloid Leukemia Patients

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Enrolling; Phase 3

Conditions: AML, Adult

Treatments: Drug: Azacitidine; Drug: Daunorubicin/Idarubicin; Drug: Cytarabine; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT07132684

IIT2025095

Details and patient eligibility

About

This study is a multicenter, randomized, controlled phase III clinical trial aimed at comparing the efficacy of two induction chemotherapy regimens-VA (Venetoclax + Azacitidine) and D/IA (Daunorubicin/Idarubicin + Cytarabine)-in elderly patients (aged 60-75) with acute myeloid leukemia (AML) who are fit for intensive chemotherapy.

Enrollment: 240 estimated patients

Sex: All

Ages: 60 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of AML according to WHO (2022) or ICC criteria.

• Age ≥60 and ≤75 years.

• ECOG performance status score of 0-2.

• Adequate organ function:

  • Total bilirubin ≤1.5× upper limit of normal (ULN)
  • AST and ALT ≤2.5× ULN
  • Serum creatinine <2× ULN
  • Cardiac enzymes <2× ULN
  • Left ventricular ejection fraction (LVEF, by echocardiogram) within normal range Signed informed consent by the patient or legal representative.

Exclusion criteria

• Acute promyelocytic leukemia with PML-RARA fusion gene.
• AML with RUNX1-RUNX1T1 or CBFB-MYH11 fusion genes.
• AML with BCR-ABL fusion gene.
• Relapsed or refractory AML (previously treated with induction chemotherapy, but hydroxyurea is allowed).
• Concurrent other malignancies requiring treatment.
• Active cardiac disease (e.g., uncontrolled angina, recent myocardial infarction, severe arrhythmias, uncontrolled heart failure, LVEF below normal).
• Severe infectious diseases (e.g., untreated tuberculosis, pulmonary aspergillosis).
• Other conditions deemed unsuitable by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

D/IA (Daunorubicin/Idarubicin + Cytarabine)

Active Comparator group

Description:

Induction Cycle 1: * Cytarabine: 100 mg/m²/day, days 1-7 * Daunorubicin: 60 mg/m²/day, days 1-3 or * Idarubicin: 12 mg/m²/day, days 1-3 • Induction Cycle 2 (if CR/CRi/CRh not achieved after Cycle 1): * Cyclophosphamide: 350 mg/m²/day, days 2 and 5o Cytarabine: 100 mg/m²/day, days 1-7 * Daunorubicin: 45 mg/m²/day, days 1-2 or * Idarubicin: 8 mg/m²/day, days 1-2 Consolidation Therapy • Intermediate-Dose Cytarabine (ID-Ara-C): 2 cycles Ara-C 1g/m² Q12h, d1-3 (aged ≥60 and \<70 years) or Ara-C 500mg/m² Q12h d1-3 (aged ≥70 years) Maintenance Therapy * Low/Intermediate-Risk Patients: 1. DA/IA "2+5" Regimen, 2 cycles Cytarabine: 100 mg/m²/day, days 1-5 Daunorubicin: 30 mg/m²/day, days 1-2 or Idarubicin: 8 mg/m²/day, days 1-2 2. VA Regimen, 4 cycles Azacitidine: 75 mg/m²/day, days 1-5 Venetoclax: 400 mg/day, days 1-7, oral * High-Risk Patients: VA Regimen, 6 cycles Allogeneic Transplantation: Recommended for high-risk patients and those with persistent MRD positivity.

Treatment:

Drug: Venetoclax

Drug: Cytarabine

Drug: Daunorubicin/Idarubicin

Drug: Azacitidine

VA Regimen

Experimental group

Description:

Induction Cycles * Azacitidine: 75 mg/m²/day, days 1-7 * Venetoclax: Day 1: 100 mg Day 2: 200 mg Days 3-21: 400 mg/day If bone marrow blasts \>5% on day 21, extend to day 28 with 400 mg/day • Efficacy will be assessed after 2 cycles. If CR/CRi/CRh is not achieved but the investigator believes continued treatment is beneficial, up to 4 cycles may be administered. Consolidation Therapy • Intermediate-Dose Cytarabine (ID-Ara-C): 2 cycles Ara-C 1g/m² Q12h, d1-3 (aged ≥60 and \<70 years) or Ara-C 500mg/m² Q12h d1-3 (aged ≥70 years) Maintenance Therapy * Low/Intermediate-Risk Patients: 1: DA/IA "2+5" Regimen, 2 cycles Cytarabine: 100 mg/m²/day, days 1-5 Daunorubicin: 30 mg/m²/day, days 1-2 or Idarubicin: 8 mg/m²/day, days 1-2 2.VA Regimen, 4 cycles Azacitidine: 75 mg/m²/day, days 1-5 Venetoclax: 400 mg/day, days 1-7, oral * High-Risk Patients: * VA Regimen, 6 cycles Allogeneic Transplantation: Recommended for high-risk patients and those with persistent MRD positivity.

Treatment:

Drug: Venetoclax

Drug: Cytarabine

Drug: Azacitidine