The Efficacy and Safety of Homoharringtonine Combined With Venetoclax and Azacitidine Versus Standard Chemotherapy or VA in the Treatment of Acute Myeloid Leukemia With High-risk, a Multicenter, Prospective, Randomized Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 876
- 试验地点
- 1
- 主要终点
- Composite complete remission (CRc)
研究概览
简要总结
The aim of this study is to evaluate the safety and efficacy of homohartonine combined with venetoclax and azacitidine (HVA) versus intensive chemotherapy (IA/DA) or venetoclax combined with azacitidine (VA) in newly diagnosed high-risk AML patients.
详细描述
The HVA regimen exerts a synergistic pro-apoptotic effect and has demonstrated significant clinical efficacy against R/R AML and also overcomes adaptive resistance observed in the VA regimen. Exploratory work with small sample sizes in first-line settings suggests that combination of HHT and Ven+AZA exhibits potent anti-AML effects with good safety profiles, particularly in overcoming the impact of high-risk factors associated with AML relative to standard treatments. This indicates its potential as a more ideal option for the treatment of newly diagnosed AML with high risk factors. Therefore a prospective, multi-center, randomized controlled clinical study is planned to evaluate the efficacy and safety of the HVA regimen compared to intensive chemotherapy (IA/DA) or Venetoclax plus azacitidine (VA) regimens in newly diagnosed high-risk fit-AML or unfit AML patients.
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
- •According to the world health organization (WHO) classification of newly diagnosed with AML patients;
- •Age ≥18 years old;
- •High-risk patients should meet any of the following criteria: ① High risk group according to the European Leukemia Risk stratification (ELN) 2022; (2) Secondary AML (sAML) which develops from myelodysplastic syndrome (MDS), bone marrow hyperplastic tumor (MPN) or chronic myeloid cell leukemia, et.; (3) Treatment-related AML (t-AML), Patients have a history of cytotoxic treatment record or ionizing radiation therapy.
- •Patients did not receive anti-AML therapy (except leukopenia therapy, such as hydroxyurea or cytarabine < 1.0g/d) after the diagnosis of AML;
- •Expected survival ≥12 weeks;
- •The eastern tumor cooperation group (ECOG) score 3 points or less;
- •Kidney function: creatinine clearance acuity 30 ml/min;
- •Liver function: ALT < 5 times normal value, bilirubin < 3 times normal value;
- •Sign the informed consent form and understand and abide by the plan calls for process.
排除标准
- •Acute promyelocytic leukemia;
- •With central nervous system leukemia (CNSL) ;
- •The cardiac function > level 2;
- •The AIDS virus (HIV) infection;
- •Other clinical significance of uncontrolled condition, including but not limited to: (1) out of control, or active systemic infection (viruses, bacteria or fungi); (2) chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; (3) need to actively deal with the merger of the second tumor;
- •Can't take oral treatment or having a gastrointestinal disease impact ing the absorption;
- •Being allergy to the experimental drugs;
- •Pregnant and lactating women;
- •Patients who could not understand or adhere to the study protocol;
- •Patients deemed by the investigator to be ineligible for enrollment.
研究组 & 干预措施
IC regiment for Fit-AML
干预措施: Standard Chemotherapy (Drug)
HVA regiment for Fit-AML
干预措施: HVA (Drug)
VA regiment for unfit-AML
干预措施: VA (Drug)
HVA regiment for unfit-AML
干预措施: HVA (Drug)
结局指标
主要结局
Composite complete remission (CRc)
时间窗: At the end of cycle 2 (each cycle is 28 days).
CRc includes complete remission (CR) and complete remission accompanied with with incomplete count recovery (CRi).
次要结局
- Complete remission (CR)(At the end of cycle 2 (each cycle is 28 days).)
- Overall response rate (ORR)(At the end of cycle 2 (each cycle is 28 days).)
- DOR(1 year)
- Rate of Measurable residual disease (MRD) negative(At the end of cycle 2 (each cycle is 28 days).)
- Overall survival (OS)(1 year)
- Event-free survival (EFS)(1 year)
- Adverse events (AE)(The first dose until 28 days after treatment discontinuation)