A Multicenter, Randomized, Controlled Clinical Trial Comparing VA and D/IA Induction Regimens in Elderly Patients With Acute Myeloid Leukemia Suitable for Intensive Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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.
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
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of AML according to WHO (2022) or ICC criteria.
- •Age ≥60 and ≤75 years.
- •ECOG performance status score of 0-
- •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.
排除标准
- •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.
研究组 & 干预措施
D/IA (Daunorubicin/Idarubicin + 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:
- 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
- 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.
干预措施: Daunorubicin/Idarubicin (Drug)
D/IA (Daunorubicin/Idarubicin + 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:
- 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
- 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.
干预措施: Cytarabine (Drug)
D/IA (Daunorubicin/Idarubicin + 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:
- 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
- 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.
干预措施: Azacitidine (Drug)
D/IA (Daunorubicin/Idarubicin + 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:
- 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
- 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.
干预措施: Venetoclax (Drug)
VA Regimen
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.
干预措施: Cytarabine (Drug)
VA Regimen
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.
干预措施: Azacitidine (Drug)
VA Regimen
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.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: up to 1 years after completion of enrollment
Time from randomization to death from any cause.
次要结局
- Composite Complete Remission Rate (CR/CRh/CRi)(Six weeks after induction therapy)
- MRD Negativity Rate(up to 1 years after completion of enrollment)
- Relapse-Free Survival (RFS)(up to 1 years after completion of enrollment)
- Event-Free Survival (EFS)(up to 1 years after completion of enrollment)
- 30-Day and 60-Day Mortality Rates(within 30 and 60 days of starting treatment.)