A Multicenter, Prospective, Randomized Controlled Study Comparing the Efficacy and Safety of CLAG(Cladribine, Cytarabine and G-CSF) Combined With Venetoclax and CLAG in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 172
- 试验地点
- 1
- 主要终点
- Composite Complete remission (cCR, CR+CRi)
研究概览
简要总结
This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) AML.
详细描述
The efficacy and prognosis of relapsed/refractory(r/r) AML are very poor, and there is no standard chemotherapy regimen were defined for r/r AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells. Previous studies have confirmed the efficacy of cladribine in the treatment of r/r AML, with a response rate of 30-45%.Our previous experience has shown that CLAG in combination of venetoclax are effective with tolerable toxicity profiling. However, there is a lack of multicenter, prospective, randomized controlled trials to further confirm the results. Therefore, a clinical study is planned to evaluate the efficacy and safety of CLAG+VEN compared to CLAG in r/r AML who were eligible for intensive therapy.
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
- •Diagnosed of AML according to the World Health Organization (WHO) classification.
- •All patients should aged 18 to 65 years.
- •Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
- •Diagnostic criteria for relapsed AML: Leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) after CR, or leukemia cell infiltration appears outside the marrow.
- •Diagnostic criteria for refractory AML: The newly diagnosed patients who failed to respond to two courses of standard treatment; Patients who relapsed within 12 months after consolidation intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia.
- •The score of Eastern Cooperative Oncology Group (ECOG) is 0-
- •Renal function: creatinine clearance rate ≥ 30ml/min.
- •Liver function: ALT<5 times normal value, bilirubin<3 times normal value.
- •Predicted survival ≥ 3 months.
- •Able to accept oral Venetoclax.
- •Sign an informed consent form and be able to understand and follow the procedures required by this protocol.
排除标准
- •Diagnosed of acute promyelocytic leukemia (AML-M3)
- •Patients with central nervous system (CNS) invasion.
- •Cardiac function < grade
- •Known human immunodeficiency virus (HIV) infection.
- •Other clinically significant uncontrolled conditions, including but not limited to: a. uncontrolled or active systemic infections (viruses, bacteria, or fungi); b. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; c. Secondary tumors requiring active treatment.
- •Allergy to experimental drugs.
- •Pregnant and lactating women.
- •Patients who ineligible for the study according to the investigator's assessment.
研究组 & 干预措施
CLAGV regimen
CLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax.
Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: Cladribine (Drug)
CLAGV regimen
CLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax.
Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: Cytarabine (Drug)
CLAGV regimen
CLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax.
Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: G-CSF (Drug)
CLAGV regimen
CLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax.
Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: Venetoclax (Drug)
CLAG regimen
CLAG regimen for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF.
Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: Cladribine (Drug)
CLAG regimen
CLAG regimen for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF.
Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: Cytarabine (Drug)
CLAG regimen
CLAG regimen for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF.
Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined.
干预措施: G-CSF (Drug)
结局指标
主要结局
Composite Complete remission (cCR, CR+CRi)
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Will compare composite complete remission(CR+CRi: complete response \[CR\] and complete response with incomplete blood count recovery \[CRi\]) between CLAGV regimen and CLAG regimen
次要结局
- Relapse free survival(RFS)(1 year post treatment)
- Duration of completed response(DoR)(1 year post treatment)
- Overall Response rate (ORR)(At the end of Cycle 1 (each cycle is 28 days))
- MRDneg CR rate(At the end of Cycle 1 (each cycle is 28 days))
- Overall Survival(OS)(1 year post treatment)
- Relapse rate(1 year post treatment)
- Incidence of Adverse Events(Duration of treatment, up to 1 year)