A Phase 2/3 Prospective, Randomized, Controlled, Parallel Group Study of Intensive Therapy Combined With Venetoclax for Newly Diagnosed Adult Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 312
- 试验地点
- 1
- 主要终点
- Event-free survival
研究概览
简要总结
300 patients will be randomly distributed into the control group (n=150) and the experimental group(n=150). Patients will receive two cycles of induction chemotherapy. The control group receives standard 3+7 induction regimen containing cytarabine (100mg/m2 d1-7) and daunorubicin (60mg/m2 d1-3). The experimental group receives venetoclax combined with intensive chemotherapy (3+7 induction regimen same as the control group). For each group, patients who fail to achieve CR/CRi after two courses of induction therapy may receive alternative therapy decided by their physicians. After CR/CRi achieved, subjects proceed allo-transplantation or consolidation therapy according to their ELN risks: subjects in favorable risk group should continue with chemotherapy; subjects in poor risk group should go through transplantation; for subjects in intermediate risk group, those with suitable donors can receive transplantation while others can continue with consolidation therapy. Subjects receive 3 courses of intermediate-dose cytarabine (1.5g/m2 q12h d1, 3, 5) for age>55 years or high dose cytarabine (3g/m2 q12h d1, 3, 5) for age≤ 55 years as consolidation therapy with venetoclax in experimental group and without venetoclax in control group. After consolidation, patients will be observed.
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
- •Patients with newly diagnosed AML (except for APL subtype) according to 2016 World Health Organization (WHO) classification and have not received chemotherapy before.
- •Age ≥18 years and ≤65 years.
- •Patient considered eligible for intensive chemotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at randomization.
- •Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of norm (ULN) or creatinine clearance >40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR).
- •Adequate hepatic function as evidenced by:(1) Serum total bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's disease, or leukemic involvement following approval by the Coordinating Investigator or Trial Coordinator;(2) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN, unless considered due to leukemic involvement following approval by the Coordinating Investigator or Trial Coordinator;(3)Myocardial enzyme<2.0×upper limit normal;(4)Left ventricular ejection fraction are within the normal range by measure of echocardiogram (ECHO)
- •No prior chemotherapy for AML except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts > 25x109/L).
- •Able to understand and willing to sign an informed consent form (ICF).
排除标准
- •AML with BCR-ABL1; or myeloid blast crisis of CML.
- •Subjects who have received a prior treatment for AML with chemotherapy , hypomethylating agents or venetoclax before.
- •Subjects with acute panmyelosis with myelofibrosis or myeloid sarcoma defined by WHO
- •Subjects with a prior history of MDS, MPN or MDS/MPN.
- •Subjects with other concurrent malignant tumors on treatment with the exception of basal or squamous cell carcinoma of the skin,carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding of prostate cancerand need treatment.
- •Pregnant or lactating women.
- •Active heart disease, defined as anyone of the followings:(1) Uncontrolled or symptomatic angina pectoris;(2) A myocardial infarction 6 months before enrolled; (3)Arrhythmia needed medication or with severe clinical symptoms;(4)Uncontrolled or symptomatic congestive heart failure (NYHA> grade 2);(5)Left ventricular ejection fraction below the lower limit of the normal range.
- •Subjects with an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
- •Subjects with an active viral infection caused by HIV, hepatitis B or hepatitis C virus that cannot be controlled by treatment.
- •Subjects with evidence of central nervous system leukemia before treatment.
- •Subjects with epilepsy which needs drug treatment, dementia, or other abnormal mental state that can't understand or follow the protocol.
- •Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.
研究组 & 干预措施
Venetoclax combined with intensive chemotherapy
The experimental group receives two cycles of inducation chemotherapy consisting of venetoclax combined with standard DA 3+7 regimen. After CR/CRi achieved, subjects proceed allo-transplantation or consolidation therapy according to their ELN risks. The consolidation chemotherapy regimen consists of three cycles of intermediate （for age>55 years）or high（for age≤ 55 years） dose cytarabine combined with venetoclax.
干预措施: with or without venetoclax (Drug)
Intensive chemotherapy only
The control group receives two cycles of inducation chemotherapy consisting of standard DA 3+7 regimen without venetoclax. After CR/CRi achieved, subjects proceed allo-transplantation or consolidation therapy according to their ELN risks. The consolidation chemotherapy regimen consists of three cycles of intermediate （for age>55 years）or high（for age≤ 55 years） dose cytarabine without venetoclax.
干预措施: with or without venetoclax (Drug)
结局指标
主要结局
Event-free survival
时间窗: up to 12 months
The time from randomization to treatment failure, death from any cause or relapse after achieving CR or CRi, whichever occurs first.
次要结局
- Overall survival Overall survival(up to 36 months)
- Relapse free survival(up to 36 months)
- Frequency and severity of AEs(up to 8 months)
- CR rate(up to 2 months)
- Rates of remission (CR/CRi) without measurable residual disease (CRMRD-)(up to 2 months)
- Cumulative incidence of relapse(up to 36 months)