A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of the LDA, LHAA, and DA Regimens in Young Adults With Low-Risk Acute Myeloid Leukemia Eligible for Intensive Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 267
- 试验地点
- 1
- 主要终点
- 2-year event-free survival (EFS) rate
研究概览
简要总结
This is a phase II/III, multicenter, randomized, three-arm, open-label, parallel controlled trial. The primary objective of this study is to compare the 2-years EFS rate of the LDA, LHAA, and DA regimens in newly diagnosed patients with low-risk acute myeloid leukemia who are eligible 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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed acute myeloid leukemia (AML) confirmed according to the World Health Organization (WHO) classification;
- •Classified as intermediate- or adverse-risk AML based on the European LeukemiaNet (ELN) 2022 genetic risk stratification;
- •Age 18-65 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- •Adequate hepatic and renal function: total bilirubin ≤2 mg/dL (35 μmol/L); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2× the upper limit of normal; serum creatinine ≤177 μmol/L;
- •Normal cardiac function, defined as left ventricular ejection fraction (LVEF) >50%;
- •Life expectancy ≥3 months;
- •Signed written informed consent by the patient or their legally authorized representative prior to study enrollment.
排除标准
- •Acute promyelocytic leukemia;
- •Central nervous system involvement by leukemia;
- •History of other malignancies within the past 5 years;
- •Positive for human immunodeficiency virus (HIV);
- •Presence of any other serious medical condition that may limit study participation, including advanced infections, uncontrolled diabetes mellitus, severe cardiac insufficiency, or angina;
- •Ineligible for intensive chemotherapy due to poor general condition;
- •Pregnant or breastfeeding women;
- •Inability to understand or comply with the study protocol;
- •Inability to take oral medication or presence of malabsorption syndrome;
- •Prior treatment with B-cell lymphoma 2 (BCL-2) inhibitors or hypomethylating agents, or current participation in any other investigational drug study;
- •Inability or unwillingness to provide written informed consent.
研究组 & 干预措施
Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction chemotherapy with lisaftoclax, daunorubicin, and cytarabine.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+daunorubicin+cytarabine (Drug)
Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction chemotherapy with lisaftoclax, daunorubicin, and cytarabine.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+cytarabine (Drug)
Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction chemotherapy with lisaftoclax, daunorubicin, and cytarabine.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+azacitidine (Drug)
Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction chemotherapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin (Drug)
Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction chemotherapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+cytarabine (Drug)
Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction chemotherapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+azacitidine (Drug)
Arm C: Daunorubicin+cytarabine
Participants received induction chemotherapy with daunorubicin and cytarabine.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Daunorubicin+cytarabine (Drug)
Arm C: Daunorubicin+cytarabine
Participants received induction chemotherapy with daunorubicin and cytarabine.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+cytarabine (Drug)
Arm C: Daunorubicin+cytarabine
Participants received induction chemotherapy with daunorubicin and cytarabine.
Patients achieving partial response (PR) with a reduction in bone marrow blasts >60% were allowed to receive one additional cycle of the same regimen.
Patients who achieved complete response received consolidation therapy with lisaftoclax in combination with intermediate-dose cytarabine for 3 cycles.
After completion of consolidation therapy, next-generation sequencing (NGS) was performed. Patients with minimal residual disease (MRD) negativity did not receive maintenance therapy, whereas patients with MRD positivity proceeded to maintenance therapy.
Maintenance therapy consisted of lisaftoclax in combination with azacitidine, administered for up to 1 year or 10 cycles, whichever occurred first.
干预措施: Lisaftoclax+azacitidine (Drug)
结局指标
主要结局
2-year event-free survival (EFS) rate
时间窗: from randomization up to 2 years after randomization
defined as the proportion of patients remaining free of treatment failure, hematologic relapse, MRD relapse, or death within 2 years after randomization.
次要结局
- Complete Response (CR) rate after 1/2 treatment cycles(At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days))
- Composite Complete Response (CRc) rate after 1/2 treatment cycles(At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days))
- Minimal residual disease (MRD) negativity rate after 1-2 cycles of induction chemotherapy(At the end of Cycle 1 or Cycle 2 induction chemotherapy (each cycle is 28 days))
- 2-year overall survival rate (OS)(from randomization up to 2 years)
- 2-year relapse-free survival (RFS) rate(from the date of complete remission (CR/CRi) up to 2 years after achieving response)
- Safety and Tolerability(up to 24 months)
研究者
Huafeng Wang
Principal Investigator
First Affiliated Hospital of Zhejiang University