A Multicenter, Randomized, Controlled Clinical Trial of Chidamide Combined With Venetoclax and Azacitidine in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Who Are Not Suitable for Intensive Chemotherapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 184
- 试验地点
- 1
- 主要终点
- Composite complete remission rate
研究概览
简要总结
To evaluate the feasibility, effectiveness and safety of chidamide combined with venetoclax and azacitidine in the treatment of newly diagnosed acute myeloid leukemia (AML) who are not suitable for intensive chemotherapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •（1）Age ≥18 years old, no gender limit ;
- •（2）be diagnosed with AML (non-M3) according to WHO 2016 standards;
- •（3）No previous treatment;
- •（4）Ineligible for intensive chemotherapy based on the following definitions: ≥75 years of age or 18 to 74 years of age with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 A history of cardiac disease such as congestive heart failure Treatment is required, or ejection fraction ≤ 50%, or chronic stable angina, diffusing capacity of lung for carbon monoxide (DLCO) ≤ 65%, or forced expiratory volume in first second (FEV1) ≤ 65%, creatinine clearance ≥ 30 mL/min to < 45 mL/min, moderate hepatic impairment, total bilirubin > 1.5 to ≤ 3.0 × ULN, other comorbidities that are not suitable for intensive chemotherapy in the physician's judgment.
- •（5）Subjects must have an ECOG performance status score of: 0 to 2 for subjects aged ≥ 75 years or 0 to 3 for subjects aged ≥ 18 to 74 years.
- •（6）Other comorbidities that are not suitable for intensive chemotherapy in the doctor's judgment;
- •（7）Expected survival time ≥3 months;
- •（8）Have the ability to understand and be willing to sign the informed consent form for this study.
排除标准
- •(1) Combined with other malignant tumors
- •(2) Have ever received treatment with chidamide and / or venetoclax or azacitidine;
- •(3) The risk is assessed as low risk according to the NCCN 2022 guidelines [t(8;21)(q22;q22.1);RUNX1-RUNX1T1, inv(16)(p13.1q22) or t(16;16 )(p13.1;q22);CBFB-MYH11 ] ;
- •(4) The subject is known to have AML central nervous system (CNS) infiltration;
- •(5) Have undergone cardiac angioplasty or stent placement within 12 months before signing the informed consent form , or have a history of myocardial infarction, unstable angina, or other clinically significant heart disease;
- •(6 ) Active infections (including bacterial, fungal or viral infections) and organ bleeding that cannot be controlled clinically;
- •(7) Pregnant or lactating women;
- •(8) Participated in any other clinical research within 3 months before signing the informed consent form ;
- •(9 ) The researcher believes that it is not suitable to participate in this study;
研究组 & 干预措施
Chidamide combined with venetoclax, azacitidine group
Chidamide (C): 30 mg/d orally on d1, 4, 8, 11 or 10 mg QD, d1-d14, adjusted according to patient tolerance Azacitidine (A): 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax (V): 100 mg d1 200 mg d 2 400 mg d3-d28 Orally
A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).
干预措施: Chidamide (Drug)
Chidamide combined with venetoclax, azacitidine group
Chidamide (C): 30 mg/d orally on d1, 4, 8, 11 or 10 mg QD, d1-d14, adjusted according to patient tolerance Azacitidine (A): 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax (V): 100 mg d1 200 mg d 2 400 mg d3-d28 Orally
A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).
干预措施: Venetoclax (Drug)
Chidamide combined with venetoclax, azacitidine group
Chidamide (C): 30 mg/d orally on d1, 4, 8, 11 or 10 mg QD, d1-d14, adjusted according to patient tolerance Azacitidine (A): 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax (V): 100 mg d1 200 mg d 2 400 mg d3-d28 Orally
A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).
干预措施: azacitidine (Drug)
venetoclax, azacitidine group
azacitidine: 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax: 100 mg day 1, 200 mg day 2, 400 mg day 3-d28 orally A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).
干预措施: Venetoclax (Drug)
venetoclax, azacitidine group
azacitidine: 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax: 100 mg day 1, 200 mg day 2, 400 mg day 3-d28 orally A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).
干预措施: azacitidine (Drug)
结局指标
主要结局
Composite complete remission rate
时间窗: 2 months
Composite complete remission rate after 2 cycles of treatment \[Complete remission, CR) + complete remission with incomplete blood count (CR with incomplete blood count recovery, CRi); CR + CRi \]
次要结局
- Overall response rate (ORR)(24months)
- Overall survival (OS)(24months)
- MRD response rate(24months)
研究者
Wei Hui, MD
Director
Institute of Hematology & Blood Diseases Hospital, China