Comparison of VA and D/IA Induction Regimens in Elderly Fit Acute Myeloid Leukemia Patients
Not Applicable
Not yet recruiting
- Conditions
- AML, Adult
- Interventions
- Registration Number
- NCT07132684
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 240
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description D/IA (Daunorubicin/Idarubicin + Cytarabine) Daunorubicin/Idarubicin 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. D/IA (Daunorubicin/Idarubicin + Cytarabine) Cytarabine 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. D/IA (Daunorubicin/Idarubicin + Cytarabine) Azacitidine 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. D/IA (Daunorubicin/Idarubicin + Cytarabine) Venetoclax 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. VA Regimen Cytarabine 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. VA Regimen Azacitidine 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. VA Regimen Venetoclax 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) up to 1 years after completion of enrollment Time from randomization to death from any cause.
- Secondary Outcome Measures
Name Time Method Composite Complete Remission Rate (CR/CRh/CRi) Six weeks after induction therapy Proportion of patients achieving CR, CRh, or CRi after induction.
MRD Negativity Rate up to 1 years after completion of enrollment Proportion of patients achieving MRD negativity after induction and overall treatment.
Relapse-Free Survival (RFS) up to 1 years after completion of enrollment Time from achieving CR/CRh/CRi to relapse or death.
Event-Free Survival (EFS) up to 1 years after completion of enrollment Time from randomization to treatment failure, relapse, or death.
30-Day and 60-Day Mortality Rates within 30 and 60 days of starting treatment. Proportion of patients who die within 30 and 60 days of starting treatment.