Phase II Study of Venetoclax Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Cladribine Plus LDAC Alternating With 5-Azacitidine With Venetoclax in Patients With Untreated AML
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 145
- 试验地点
- 1
- 主要终点
- Rate of complete response (CR/complete response with incomplete recovery [CRi])
研究概览
简要总结
This phase II trial studies how well venetoclax, cladribine, low dose cytarabine, and azacitidine work in treating patients with acute myeloid leukemia that has previously not been treated. Drugs used in chemotherapy, such as venetoclax, cladribine, and low dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, cladribine, low dose cytarabine induction followed by cladribine, low dose cytarabine, and azacitidine consolidation may work better in treating patients with acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVE:
I. To assess the complete response (CR/complete response with incomplete recovery [CRi]) rate of patients with acute myeloid leukemia (AML) treated with venetoclax combined with cladribine (2-CDA) plus low-dose cytarabine (LDAC) alternating with 5-azacytidine.
SECONDARY OBJECTIVES:
I. To assess overall survival (OS) of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.
II. To assess the disease free survival (DFS) patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine and achieved a complete response (CR/CRi).
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with previously untreated acute myeloid leukemia (AML). Prior therapy with hydroxyurea, hematopoietic growth factors, HMA, ATRA, or a total dose of cytarabine up to 2g (for emergency use for stabilization) is allowed.
- •Age >/= 50 years. Participants aged < 50 years who are unsuitable for standard induction therapy may be eligible after discussion with primary investigator
- •Adequate organ function as defined below:
- •liver function (bilirubin < 2mg/dL, AST and/or ALT <3 x ULN). Unless liver enzyme abnormalities are determined by the treating MD and PI to be due to leukemic infiltration.
- •kidney function (creatinine < 1.5 x ULN ).
- •ECOG performance status of ≤
- •A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- •Participants must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the participants is required prior to their enrollment on the protocol.
排除标准
- •Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Participants with documented hypersensitivity to any of the components of the chemotherapy program.
- •Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
- •Prior therapy with venetoclax
- •Participants with a diagnosis of acute promyelocytic leukemia (AML-M3) will be excluded from this study.
研究组 & 干预措施
Treatment (cladribine, cytarabine, venetoclax, azacitidine)
See Detailed Description.
干预措施: Cladribine (Drug)
Treatment (cladribine, cytarabine, venetoclax, azacitidine)
See Detailed Description.
干预措施: Azacitidine (Drug)
Treatment (cladribine, cytarabine, venetoclax, azacitidine)
See Detailed Description.
干预措施: Cytarabine (Drug)
Treatment (cladribine, cytarabine, venetoclax, azacitidine)
See Detailed Description.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Rate of complete response (CR/complete response with incomplete recovery [CRi])
时间窗: Up to completion of cycle 2 (each cycle is 28 days)
The optimum two-stage design will be implemented. Will be estimated along with the 95% confidence intervals.
次要结局
- Overall response rate(Up to 5 years)
- Overall survival (OS)(Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years)
- Disease-free survival (DFS)(Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years)
- Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0(Up to 5 years)