A Multicenter, Prospective, Randomized Controlled Clinical Study Comparing the Efficacy of LDA, LHAA, and LA Regimens in Young Adults With Intermediate- and High-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
- 450
- 试验地点
- 1
- 主要终点
- 2-year overall survival rate (OS)
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 OS rate of the LDA, LHAA, and LA regimens in newly diagnosed patients with intermediate- and high-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
- 15 Years 至 65 Years（Child, 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 (see Appendix Table 1);
- •Age 15-65 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 therapy with lisaftoclax, daunorubicin, and cytarabine.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were classified as post-transplant or non-transplant. Post-transplant patients were randomized 1:1 to receive either lisaftoclax plus azacitidine or azacitidine alone. Non-transplant patients received lisaftoclax in combination with azacitidine.
Maintenance therapy was administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity.
干预措施: Lisaftoclax+daunorubicin+cytarabine (Drug)
Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction therapy with lisaftoclax, daunorubicin, and cytarabine.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were classified as post-transplant or non-transplant. Post-transplant patients were randomized 1:1 to receive either lisaftoclax plus azacitidine or azacitidine alone. Non-transplant patients received lisaftoclax in combination with azacitidine.
Maintenance therapy was administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity.
干预措施: Lisaftoclax+ cytarabine (Drug)
Arm A: Lisaftoclax+Daunorubicin+Cytarabine
Participants received induction therapy with lisaftoclax, daunorubicin, and cytarabine.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were classified as post-transplant or non-transplant. Post-transplant patients were randomized 1:1 to receive either lisaftoclax plus azacitidine or azacitidine alone. Non-transplant patients received lisaftoclax in combination with azacitidine.
Maintenance therapy was administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity.
干预措施: Lisaftoclax+azacitidine or azacitidine (Drug)
Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction therapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy.
All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.
干预措施: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin (Drug)
Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction therapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy.
All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.
干预措施: Lisaftoclax+ cytarabine (Drug)
Arm B: Lisaftoclax+homoharringtonine+cytarabine+aclarubicin
Participants received induction therapy with lisaftoclax, homoharringtonine, cytarabine, and aclarubicin.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy.
All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.
干预措施: Lisaftoclax+azacitidine or azacitidine (Drug)
Arm C:Lisaftoclax+ azacitidine
Participants received induction therapy with lisaftoclax in combination with azacitidine.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy.
All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.
干预措施: Lisaftoclax+azacitidine (Drug)
Arm C:Lisaftoclax+ azacitidine
Participants received induction therapy with lisaftoclax in combination with azacitidine.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy.
All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.
干预措施: Lisaftoclax+ cytarabine (Drug)
Arm C:Lisaftoclax+ azacitidine
Participants received induction therapy with lisaftoclax in combination with azacitidine.
Patients with partial response (PR) or >60% reduction in bone marrow blasts were allowed to receive one additional induction cycle.
Patients achieving complete response received consolidation therapy with lisaftoclax and intermediate-dose cytarabine for 3 cycles.
For maintenance therapy, patients were stratified according to transplantation status (post-transplant or non-transplant). Post-transplant patients were randomized 1:1 to receive either combination therapy or azacitidine monotherapy. Non-transplant patients received combination maintenance therapy.
All maintenance therapies were administered for up to 1 year or 10 cycles, whichever occurred first, or until the occurrence of grade ≥4 hematologic toxicity, and were interrupted until recovery to grade ≤2.
干预措施: Lisaftoclax+azacitidine or azacitidine (Drug)
结局指标
主要结局
2-year overall survival rate (OS)
时间窗: from randomization up to 2 years
defined as the proportion of patients who were still alive from the time of randomization for the last patient until 24 months later
次要结局
- Complete Response (CR) rate after 1/2 treatment cycles(At the end of Cycle 1 or Cycle 2 of 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 of 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 of induction chemotherapy (each cycle is 28 days))
- 2-year event-free survival (EFS) rate(from randomization up to 2 years after randomization)
- 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