A Prospective,Randomized,and Comparative Study on the Efficacy of Venetoclax Combined With CACAG Regimen and BAT Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) after 1 course of treatment
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of venetoclax combined with CACAG regimen with BAT regimen in the treatment of relapsed/refractory acute myeloid leukemia.
详细描述
Despite advances in therapies for acute myeloid leukemia (AML) in the past decades, some patients still suffer from relapsed/refractory (R/R) disease, resulting in poor outcomes. With a median overall survival (OS) of 4-7 months under classic chemotherapy approaches, it is imperative to explore new treatment options.Accumulating research has demonstrated the importance of epigenetic modification in the pathogenesis of chemoresistance. Recent studies have shown that combining venetoclax with hypomethylating agents (HMAs) such as azacitidine, or low-dose cytarabine (LDAC) improves the response and survival rates in R/R AML patients. To enhance the response rate, we designed a regimen that combines chidamide, azacitidine, cytarabine, aclarubicin, and G-CSF with venetoclax (CACAG+VEN regimen) for the treatment of patients with R/R AML. In this study, we intend to compare the efficacy and safety of venetoclax combined with the CACAG regimen with Best-Available Therapy(BAT) regimen in the treatment of relapsed/refractory acute myeloid leukemia.
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 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are able to understand and willing to sign the informed consent form (ICF).
- •All patients should aged 14 to 75 years,no gender limitation.
- •Patients with R/R AML, diagnosed in accordance with the 2021 edition of the CMA criteria
- •Liver function: ALT and AST≤2.5 times the upper limit of normal ,bilirubin≤2 times the upper limit of normal;
- •Renal function: creatinine ≤the upper limit of normal;
- •Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
- •The score of Eastern Cooperative Oncology Group (ECOG) is 0-3,and the predicted survival ≥ 4 months.
- •Patients without severe allergic constitution.
排除标准
- •Patients with allergy or contraindication to the study drug;
- •Female patients who are pregnant or breast-feeding.
- •Patients with a known history of alcohol or drug addiction on the basis that there could be a higher risk of non-compliance to study treatment;
- •Patients with mental illness or other states unable to comply with the protocol;
- •Less than 6 weeks after surgical operation of important organs.
- •Liver function: ALT and AST>2.5 times the upper limit of normal ,bilirubin>2 times the upper limit of normal;Renal function: creatinine >the upper limit of normal;
- •The patient is not suitable for this clinical trial (poor compliance, substance abuse, etc.)
研究组 & 干预措施
Venetoclax Combined With CACAG Regimen
Venetoclax combined with CACAG regimen for relapsed/refractory AML. Recipients were randomized and those entering the experimental group received azacytidine,cytarabine,aclacinomycin,chidamide,venetoclax and granulocyte colony-stimulating factor. Azacytidine was used as 75 mg/m2/day from day 1 to day 7.Cytarabine was used as 75-100 mg/m2 bid from day 1 to day 5. Aclacinomycin was used as 20 mg/day on days 1,3,5. Chidamide was used as 30 mg/day on days 1,4,8,11. Venetoclax was used as 400 mg/day from day 1 to day 14.Granulocyte colony-stimulating factor was used as 300 ug/day from day 0 until agranulocytosi recovery.
干预措施: Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor (Drug)
Best-Available Therapy(BAT) Regimen
BAT regimen for relapsed/refractory AML.Recipients were randomized and those entering this group received FLAG/CLAG/MAE/DCAG/HAA/HAD regimen.
干预措施: Best-Available Therapy(BAT) Regimen (Drug)
结局指标
主要结局
Overall Response Rate (ORR) after 1 course of treatment
时间窗: 1 months after the start of study treatment
Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.
次要结局
- Complete Remission (CR) Rate after 2 courses of treatment(After two courses of chemotherapy (each course is 28 days))
- Treatment-related adverse events(From the first dose of study treatment to 30 days after the discontinuation of treatment)
- Complete Remission (CR) Rate after 1 course of treatment(2 months after study treatment)
- Rate of Minimal Residual Disease (MRD)-Negative Response(After two courses of chemotherapy (each course is 28 days))
- Early death(Within 30 days of the start of the first course of treatment)
- Overall Survival (OS)(180 days after study treatment)
- Disease-free survival(180 days after study treatment)
- Overall Response Rate (ORR) after 2 course of treatment(After two courses of chemotherapy (each course is 28 days))
- Event-free survival(180 days after study treatment)
研究者
Daihong Liu
doctor
Chinese PLA General Hospital