Venetoclax Combined With Intermediate-dose Cytarabine Versus Intermediate-dose Cytarabine for Consolidation Therapy of Acute Myeloid Leukemia (AML): a Multicenter, Prospective, Randomized Controlled, Phase 2 Study
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 232
- 试验地点
- 1
- 主要终点
- Rate of Measurable residual disease (MRD) negative
研究概览
简要总结
This study intends to use a randomized controlled design to compare the MRD-negativw rate and related efficacy and safety of venetoclax combined with intermediate-dose cytarabine (IDAC) versus IDAC in the consolidation treatment of patients with AML after remission, providing high-quality evidence-based medical evidence for optimizing post-remission consolidation therapy for AML and improving patients' prognosis.
详细描述
Studies have shown that venetoclax can significantly enhance the efficacy of intensive chemotherapy (IC) in the induction and salvage treatment of AML. However, there is still a lack of direct comparison of the efficacy and safety of venetoclax combined with intermediate-dose cytarabine (IDAC) with IDAC for consolidation in AML. In order to evaluate the benefit of venetoclax combined with IDAC, we plan to conduct a multicenter, prospective randomized controlled, phase 2 study to compare the efficacy and safety of venetoclax (d1-7, 400mg QD) combined with cytarabine (d1-3, 1.5g/㎡, q12h) versus cytarabine only for consolidation therapy in AML, aiming to fill the current evidence gap and provide scientific basis for improving deeper remission of AML and finally improve patients' long-term survival.
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
- •Age between 18 and 65 years, any gender;
- •Meet the WHO 2022 diagnostic criteria for acute myeloid leukemia (AML), and achieve complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after induction therapy. CR is defined as bone marrow blasts ≤5%, absolute neutrophil count ≥1.0×10⁹/L, and platelets ≥100×10⁹/L; CRi is defined as bone marrow blasts ≤5%, absolute neutrophil count ≥0.5×10⁹/L, and platelets ≥50×10⁹/L;
- •Baseline MRD testing (using multiparameter flow cytometry, MFC) must be completed at enrollment.
- •Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
- •Major organ function is basically normal and meets the following requirements: ① Liver function: total bilirubin ≤1.5×ULN (except patients with liver metastasis or Gilbert's syndrome), ALT and AST ≤2.5×ULN; ② Kidney function: serum creatinine ≤1.5×ULN or creatinine clearance ≥60 ml/min; ③ Cardiac function: left ventricular ejection fraction (LVEF) ≥50%;
- •The patient or their legal representative signs a written informed consent form, agrees to comply with the study protocol, and completes the specified follow-up procedures.
排除标准
- •Presence of other active malignant tumors (excluding indolent tumors that have been cured, such as basal cell carcinoma of the skin and carcinoma in situ of the cervix);
- •Central nervous system leukemia;
- •Existence of uncontrolled severe infection (such as sepsis, fungal pneumonia, active tuberculosis, etc.);
- •History of severe heart disease, including but not limited to: severe arrhythmias (such as ventricular tachycardia, atrial fibrillation with rapid ventricular rate, etc.), history of myocardial infarction (within the past 6 months), severe heart failure (NYHA functional class ≥3), etc.;
- •Women who are pregnant or breastfeeding; women planning pregnancy or men of reproductive potential who have not used effective contraception during the study and within 6 months after treatment;
- •Known allergy to venetoclax, cytarabine, or other components of the combination regimen in the study;
- •Having mental illness (such as schizophrenia, major depressive disorder, etc.) or cognitive dysfunction that prevents cooperation with study follow-up and treatment;
- •Active hepatitis B virus infection (HBV DNA positive), active hepatitis C virus infection (HCV RNA positive), or human immunodeficiency virus (HIV) infection;
- •Undergoing major surgery, radiation therapy, other chemotherapy drugs, or investigational drug treatments within 3 weeks prior to study drug treatment.
研究组 & 干预措施
VEN+IDAC
Venetoclax 400mg per day from day 1 to day 7; cytarabine 1.5g/m^2 q12h from day 1 to day 3.
干预措施: Cytarabine (Drug)
IDAC
Cytarabine 1.5g/m^2 q12h from day 1 to day 3
干预措施: Cytarabine (Drug)
VEN+IDAC
Venetoclax 400mg per day from day 1 to day 7; cytarabine 1.5g/m^2 q12h from day 1 to day 3.
干预措施: Ventoclax (Drug)
结局指标
主要结局
Rate of Measurable residual disease (MRD) negative
时间窗: At the end of cycle 2 (28 days for a cycle)
MRD is monitored using flow cytometric analysis with a positive MRD threshold of 0.1%.
次要结局
- Cumulative Incidence of Recurrence (CIR)(2 years)
- Overall survival (OS)(2 years)
- Disease Free Survival (DFS)(2 years)
- Aderse events(At the end of cycle 2 (28 days for a cycle))
- The rate of being bridged to allogeneic hematopoietic stem cell transplantation(2 years)
研究者
Qing Zhang
Chief Physician
Guangdong Second Provincial General Hospital