VISTA-AML- Venetoclax Intensity Selection Trial in AML: A Randomized Phase II Selection Trial of Venetoclax-Based Induction Intensity in Newly Diagnosed Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 320
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
This randomized, open label, multi arm phase II trial will evaluate the efficacy and safety of venetoclax based induction regimens of varying intensity (VA, VAM, or 2+5+V) versus standard 3+7 in fit patients aged ≥14 years with newly diagnosed AML. The trial is designed to select the optimal regimen as the experimental arm for a subsequent phase III randomized controlled trial.
A total of 320 patients will be enrolled in this study，and segregated into four groups with 80 in each group. Patients who achieve CR/CRi/CRh after using different induction regimens will receive the same consolidation. Allogeneic hematopoietic stem cell transplantation is recommended for patients in the high-risk group or those with persist MRD positivity. After completion of the treatment phase, patients entered the follow-up period.
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of AML per WHO (2022) or ICC criteria, and MDS/AML as defined by ICC (with bone marrow blast percentage of 10%-20%).
- •Age ≥14 years, male or female.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Judged by the investigator to be suitable for intensive induction chemotherapy and expected to tolerate the treatment intensity specified in the protocol.
- •Meet the following laboratory test requirements (assessed within 7 days prior to treatment):
- •Total bilirubin ≤1.5 × upper limit of normal (ULN) for the same age group;
- •AST and ALT ≤2.5 × ULN for the same age group;
- •Serum creatinine <2 × ULN for the same age group;
- •Cardiac enzymes <2 × ULN for the same age group;
- •Cardiac ejection fraction determined by echocardiography (ECHO) within the normal range.
- •Written informed consent must be signed before any study specific procedures are initiated, by the patient themselves or by their immediate family members. If, in consideration of the patient's medical condition, signing by the patient themselves would be detrimental to their treatment, the informed consent may be signed by the legally authorized representative or the patient's immediate family members.
排除标准
- •Acute promyelocytic leukemia with PML-RARA fusion gene.
- •Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene.
- •Acute myeloid leukemia with BCR-ABL fusion gene.
- •Presence of FLT3 mutation (these patients are recommended to be enrolled in clinical trials of FLT3 inhibitors).
- •Patients who have previously received induction chemotherapy (however, cytoreductive therapy such as hydroxyurea is permitted).
- •Concurrent malignancy of other organs that requires treatment.
- •Active cardiac disease, defined as one or more of the following:
- •History of uncontrolled or symptomatic angina pectoris;
- •Myocardial infarction within 6 months prior to study enrollment;
- •History of arrhythmia requiring medication or with clinically significant symptoms;
- •Uncontrolled or symptomatic congestive heart failure (> NYHA class 2).
- •Serious infectious diseases (e.g., active tuberculosis, pulmonary aspergillosis).
- •Patients deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
VA
Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-21, administered orally (po). Bone marrow examination is performed on day 21. If blasts >5%, then venetoclax 400 mg is continued on days 21-28.
Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,
干预措施: Venetoclax (Drug)
VAM
Drug: Liposome Mitoxantrone Liposome Mitoxantrone: 24 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,
干预措施: Venetoclax (Drug)
3+7
Drug: daunorubicin daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-3, Drug: Cytarabine Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-7,
干预措施: Daunorubicin (Drug)
2+5+V
Drug: daunorubicin daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-2, every 4 weeks Drug: Cytarabine Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-5, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 3, 200 mg on day 4, and 400 mg on days 5-11, administered orally (po)
干预措施: Cytarabine (Drug)
VAM
Drug: Liposome Mitoxantrone Liposome Mitoxantrone: 24 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,
干预措施: Liposome Mitoxantrone (Drug)
VA
Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-21, administered orally (po). Bone marrow examination is performed on day 21. If blasts >5%, then venetoclax 400 mg is continued on days 21-28.
Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,
干预措施: Azacitidine (Drug)
2+5+V
Drug: daunorubicin daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-2, every 4 weeks Drug: Cytarabine Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-5, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 3, 200 mg on day 4, and 400 mg on days 5-11, administered orally (po)
干预措施: Daunorubicin (Drug)
3+7
Drug: daunorubicin daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-3, Drug: Cytarabine Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-7,
干预措施: Cytarabine (Drug)
2+5+V
Drug: daunorubicin daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-2, every 4 weeks Drug: Cytarabine Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-5, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 3, 200 mg on day 4, and 400 mg on days 5-11, administered orally (po)
干预措施: Venetoclax (Drug)
VAM
Drug: Liposome Mitoxantrone Liposome Mitoxantrone: 24 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,
干预措施: Azacitidine (Drug)
结局指标
主要结局
Event-free survival (EFS)
时间窗: up to 3 years
It is defined as the time from the start of randomization to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first).
次要结局
- 30-day postinduction mortality(up to 30 days)
- 60-day postinduction mortality(Up to 60 days)
- Composite complete remission (CRc) rate(Up to eight weeks)
- Measurable Residual Disease (MRD) negative rate by flow cytometry(Up to eight weeks)
- Measurable Residual Disease (MRD) negative rate by molecular testing(Up to approximately eight weeks)
- Relapse-free Survival (RFS)(Up to 3 years)
- Overall survival (OS)(Up to 3 years)
- Cumulative incidence of relapse (CIR)(Up to 3 years)
- Incidence of treatment related adverse events(From day 1 of treatment to 28 days after the last dose)