A Multicenter, Randomized, Controlled Clinical Trial of Intermediate-dose HAD Regimen for CEBPA Double-mutated Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 148
- 试验地点
- 2
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
AML is highly heterogeneous in pathogenesis, and CEBPA double-mutated (CEBPAdm) AML is a common type of leukemia in China. Currently, no targeted therapies for CEBPAdm, and chemotherapy and transplantation are still the treatment options for CEBPA double-mutated AML. At present, the "3+7" treatment induction regimen of cytarabine combined with anthracyclines is still the first-line recommended regimen. In our retrospective study, the intermediate dose HAD regimen produced a 3-year RFS of 84.7% and a 3-year OS of 92.8% in CEBPAdm AML. Therefore, this project intends to confirm the efficacy of intermediate-dose HAD in the treatment of CEBPA double-mutated AML is superior to the conventional treatment regimen through the multi-center RCT study.
详细描述
This is a prospective, randomized, controlled clinical trial of patients diagnosed with CEBPA double-mutated AML. Patients who meet the inclusion criteria are randomly assigned to receive the intermediate-dose HAD regimen or the conventional 3+7 induction regimen (IA or DA), respectively. When patients reach complete remission (CR) after the induction therapy, 3 courses of the high-dose cytarabine regimen (3g/m2 q12h, 3 days) are used. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment. When patients do not achieve CR after the induction therapy, reinduction therapy with IAC (IDA 10mg/ m2 for 3 days, cytarabine 100mg/m2 for 7 days, cyclophosphamide 350mg/m2 d2, d5) regimen is used. Patients who still do not achieve CR after reinduction therapy will be removed from the group.
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
- 14 Years 至 54 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AML diagnosed according to WHO-2022 classification with recurrent CEBPA mutations and containing mutation in the bZIP domain.
- •Older than 14 years old and younger than 55 years old
- •Male or female.
- •The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of AML patients were 0-2 points.
- •Meet the following laboratory tests (performed within 7 days prior to treatment) 1) Total bilirubin ≤ 1.5 times of the upper limit of normal value (same age); 2) AST and ALT≤ 2.5 times of the upper limit of normal value (same age); 3) Blood creatinine < 2 times of the upper limit of normal value (same age); 4) Myocardial enzymes < 2 times of the upper limit of normal value (same age); 5) Echocardiography (ECHO) was performed to determine the ejection fraction of the heart within the normal range.
排除标准
- •Patients who have previously received induction chemotherapy, regardless of efficacy.
- •Simultaneously suffering from malignant tumors of other organs and requiring treatment).
- •Pregnant or lactating women. Male or female patients participating in the trial must take contraceptive measures during the trial treatment period.
- •Active heart disease, defined as one or more of the following:1) Have a history of uncontrolled or symptomatic angina pectoris;2) Myocardial infarction less than 6 months prior to enrollment in the study;3) A history of arrhythmia requiring medication treatment or severe clinical symptoms;4) Uncontrolled or symptomatic congestive heart failure (> NYHA grade 2);5) The ejection fraction is below the lower limit of the normal range.
- •Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).
- •Those who were not considered suitable for inclusion by the researchers.
研究组 & 干预措施
conventional treatment
Patients were treated with 3+7 induction regimen (IA or DA). When patients reach complete remission (CR) after the induction therapy, 3 courses of the high-dose cytarabine regimen (3g/m2 q12h, 3 days) are used. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment. When patients do not achieve CR after the induction therapy, reinduction therapy with IAC (IDA 10mg/m2 for 3 days, cytarabine 100mg/m2 for 7 days, cyclophosphamide 350mg/ m2 d2, d5) regimen is used. Patients who still do not achieve CR after reinduction therapy will be removed from the group.
干预措施: Daunorubicin+Cytarabine (Drug)
intermediate-dose HAD regimen
Patients received intermediate-dose HAD regimen. When patients reach complete remission (CR) after the induction therapy, 3 courses of the high-dose cytarabine regimen (3g/m2 q12h, 3 days) are used. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment. When patients do not achieve CR after the induction therapy, reinduction therapy with IAC (IDA 10mg/m2 for 3 days, cytarabine 100mg/m2 for 7 days, cyclophosphamide 350mg/m2 d2, d5) regimen is used. Patients who still do not achieve CR after reinduction therapy will be removed from the group.
干预措施: HAD (Drug)
结局指标
主要结局
Event-free survival (EFS)
时间窗: up to 2 years after the date of the last enrolled participants
The interval from randomization to assessment of response after the second course of chemotherapy treatment if patients failed to achieve CR after two courses of induction therapy, the date of relapse, or the date of death, whichever occurred first.
次要结局
- Complete response rate (CR)(Six weeks after induction therapy)
- 30-day mortality(Within 30 days of randomization)
- overall survival(up to 2 years after the date of the last enrolled participants)
- Relapse free survival censored at hematopoietic stem cell transplantation(up to 2 years after the date of the last enrolled participants)
- Relapse free survival(RFS)(up to 2 years after the date of the last enrolled participants)
- Event-free survival censored at hematopoietic stem cell transplantation(up to 2 years after the date of the last enrolled participants)
- 60-day mortality(Within 60 days of randomization)
- overall survival censored at hematopoietic stem cell transplantation(up to 2 years after the date of the last enrolled participants)