Venetoclax/Azacitidine/Low-Dose Cytarabine/Aclarubicin/G-CSF (VA-CAG) in Newly-Diagnosed Acute Myeloid Leukemia: A Phase-2, Multi-center, Prospective Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- CR rate
研究概览
简要总结
This study aims to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine and CAG(VA-CAG) as induction regimen in newly diagnosed young patients with acute myeloid leukemia(AML).
详细描述
This is an open-label, multicenter, phase II clinical trial to assess the therapeutic efficacy and safety of venetoclax in combination with azacitidine (VA) and CAG (G-CSF priming, low dose cytarabine, and aclarubicin) as induction regimen in newly diagnosed patients with acute myeloid leukemia (AML).
The combination of venetoclax and azacitidine is the standard therapy for elderly (> 60 year old) patients with newly diagnosed AML who are not eligible for intensive chemotherapy. Previous studies have shown that venetoclax plus intense chemotherapy represent promising efficacy in de novo AML patients with high complete remission rates and good tolerance. The preliminary results suggest that venetoclax in combination with azacitidine and CAG are well tolerated and effective for newly diagnosed young patients with AML. Thus, this phase II clinical trial is going to further explore its efficacy and safety. It is expected that about 100 patients will take part in this trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients ≥ 18 years old and ≤ 65 years old
- •Newly diagnosed as AML patients according to 2016 World Health Organization (WHO) classification;
- •Patients without receiving prior therapy for AML;
- •Eastern Cooperative Oncology Group (ECOG) Performance status score less than 3;
- •Liver function: Total bilirubin ≦2 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN
- •Renal function：Ccr（Creatinine Clearance Rate） ≧30 ml/min; Scr (serum creatinine) ≦2 ULN
- •Heart function: left ventricular ejection fraction ≧45%
- •Patients must participate in this clinical trial voluntarily and sign an informed consent form.
排除标准
- •Acute promyeloid leukemia；
- •AML with central nervous system (CNS) infiltration；
- •Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML；
- •Patients with a life expectancy <3 months
- •Patients with uncontrolled active infection;
- •HIV infection;
- •Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment; b) An active second cancer that requires treatment within 6 months of study entry.
- •Female who are pregnant, breast feeding or childbearing potential.
- •Patients deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
Treatment group
Induction: Subjects who meet the enrollment conditions will receive Venetoclax plus Azacitidine and CAG(VA-CAG) . Participants will receive this induction Therapy as azacitidine on days 1-7, venetoclax aily on days 1-28, cytarabine q12h on days 1-7, aclacinomycin on days 1,3,5,7, and granulocyte colony-stimulating factor on days 0-8. Participants will receive second induction if not reach complete remission.
Consolidation: If patients are intermediate or poor risk and have plans for allogeneic hematopoietic stem-cell transplantation(allo-HSCT) , high dose cytarabine (3g/m2 q12h days 1-3) for 1-2 cycles and follow up with allo-HSCT. In other cases, high dose cytarabine for 4 cycles.
干预措施: Venetoclax in combination with azacitidine and CAG (Drug)
结局指标
主要结局
CR rate
时间窗: At the end of Cycle 1 of induction (each cycle is about 30 days)
次要结局
- Adverse Events(From the first day of induction until the starting day of the next cycle of therapy (up to 60 days）)
- Duration of remission(From the date of the first remission until the date of relapse (assessed up to 30 months))
- Minimal Residual Disease negative remission rate (MRD-negative rate)(After 1 cycle of induction (each cycle is about 30 days))