Venetoclax, Azacitidine Combined With Homoharringtonine Versus Venetoclax and Azacitidine in Newly Diagnosed Elderly (60-75 Years) Acute Myeloid Leukemia: A Multicenter, Open-label, Randomized, Controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 308
- 试验地点
- 1
- 主要终点
- Composite Complete Remission Rate (CRc)
研究概览
简要总结
This is a multicenter, open-label, randomized, controlled phase III clinical trial designed to evaluate the efficacy and safety of the combination of Venetoclax, Azacitidine, and Homoharringtonine (VAH) compared to Venetoclax and Azacitidine (VA) alone in newly diagnosed elderly patients with Acute Myeloid Leukemia (AML).
A total of 308 treatment-naïve patients aged 60-75 years with AML (non-APL) will be enrolled and randomly assigned in a 1:1 ratio to either the control arm (VA) or the experimental arm (VAH). The study aims to determine if the addition of Homoharringtonine to the standard VA regimen can improve response rates. To mitigate bias in this open-label study, the primary and key secondary efficacy endpoints will be assessed by an Independent Review Committee or central laboratory blinded to treatment allocation.
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
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of acute myeloid leukemia (AML), non-APL, according to the 2022 International Consensus Classification (ICC) criteria.
- •Age 60 to 75 years, inclusive.
- •Life expectancy of at least 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Adequate organ function unless abnormalities are considered due to leukemic organ involvement:
- •Serum creatinine ≤ 1.5 × upper limit of normal (ULN). Oxygen saturation > 92% on room air. Total bilirubin ≤ 3.0 × ULN. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN.
- •If laboratory abnormalities are considered due to leukemic organ involvement, total bilirubin ≤ 5.0 × ULN and ALT/AST ≤ 5.0 × ULN are permitted.
- •Female subjects of childbearing potential must be postmenopausal or surgically sterile. Male subjects must agree to use effective contraception or abstain from sperm donation from study start through 90 days after the last dose of study treatment.
- •Ability to understand and voluntarily sign an informed consent form prior to any study-related procedures.
排除标准
- •Prior treatment with hypomethylating agents for myelodysplastic syndrome (MDS). Prior chemotherapy for AML, except hydroxyurea. Prior CAR-T cell therapy.
- •Prior investigational therapy for AML.
- •Documented history of myeloproliferative neoplasm (MPN).
- •Favorable-risk AML according to 2022 European LeukemiaNet (ELN) criteria.
- •Known active central nervous system (CNS) involvement of AML.
- •Known human immunodeficiency virus (HIV) infection.
- •Active hepatitis B or hepatitis C requiring antiviral therapy. Risk of hepatitis B reactivation (hepatitis B surface antigen positive or hepatitis B core antibody positive without antiviral prophylaxis).
- •History of another malignancy within 5 years prior to screening, except adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer treated with curative intent, or ductal carcinoma in situ treated with curative intent.
- •Unstable systemic disease including unstable angina, cerebrovascular accident, or transient ischemic attack within 3 months prior to screening. Myocardial infarction within 3 months prior to screening. Congestive heart failure New York Heart Association class III or IV. Recent pacemaker implantation. Severe liver, kidney, or metabolic disease requiring ongoing treatment. Pulmonary arterial hypertension. Clinically significant or uncontrolled arrhythmias including persistent atrial fibrillation or flutter, symptomatic ventricular arrhythmias, QTc ≥ 470 ms in males or ≥ 480 ms in females, second- or third-degree atrioventricular block without pacemaker, or arrhythmias requiring continuous antiarrhythmic therapy.
- •Malabsorption syndrome or any condition preventing enteral drug administration. Active systemic infection requiring treatment.
- •Significant neurological or psychiatric disorders requiring treatment including epilepsy grade 2 or higher, paralysis, aphasia, recent cerebral infarction, severe traumatic brain injury, dementia, Parkinson's disease, or schizophrenia.
- •Fertile males or females of childbearing potential unwilling to use effective contraception during treatment and for 12 months after completion of treatment.
- •White blood cell count > 25 × 10⁹/L at screening (hydroxyurea permitted to reduce count to meet eligibility).
研究组 & 干预措施
Experimental: VAH
Patients receive Venetoclax, Azacitidine, and Homoharringtonine
干预措施: Azacitidine (Drug)
Experimental: VAH
Patients receive Venetoclax, Azacitidine, and Homoharringtonine
干预措施: Venetoclax (Drug)
Experimental: VAH
Patients receive Venetoclax, Azacitidine, and Homoharringtonine
干预措施: Homoharringtonine (Drug)
Active Comparator: VA
Patients receive Venetoclax and Azacitidine
干预措施: Venetoclax (Drug)
Active Comparator: VA
Patients receive Venetoclax and Azacitidine
干预措施: Azacitidine (Drug)
结局指标
主要结局
Composite Complete Remission Rate (CRc)
时间窗: Up to approximately 8 weeks (from randomization to initiation of Cycle 3; each cycle is planned as 28 days).
The proportion of randomized participants who achieve complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), according to the 2022 ELN criteria, from randomization up to the initiation of Cycle 3.
Composite Complete Remission Rate (CRc)
时间窗: Up to approximately 12 weeks (from randomization to initiation of Cycle 4; each cycle is planned as 28 days).
The proportion of randomized participants who achieve complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), according to the 2022 ELN criteria, from randomization up to the initiation of Cycle 4. Participants who are randomized but do not undergo ELN disease assessment within this period will be considered non-responders. CR/CRi rates will be compared between treatment groups using the Cochran-Mantel-Haenszel (CMH) test, stratified by age (60-64, 65-69, 70-75 years) and study center. Two-sided 95% confidence intervals will be calculated.
次要结局
- CR/CRi Rate by Cycle 1 and Cycle 2(End of Cycle 1 and end of Cycle 2 (each cycle is planned as 28 days; assessments performed prior to initiation of Cycle 2 and Cycle 3))
- Event-Free Survival (EFS)(up to 36 months)
- Overall Survival (OS)(up to 36 months)
- CR/CRi Rate by Cycle 2 and Cycle 3(End of Cycle 1 and end of Cycle 2 (each cycle is planned as 28 days; assessments performed prior to initiation of Cycle 2 and Cycle 3))
- Complete Remission (CR) Rate(From randomization through the end of Cycle 3 (approximately 12 weeks).)
- Minimal Residual Disease (MRD) Negativity Rate(Up to 2 years after completion of treatment.)
- Time to First Composite Complete Remission (CR or CRi)(From randomization until the first documented CR or CRi during study treatment (up to approximately 12 months).)
研究者
Xianmin Song, MD
Director, Department of Hematology
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine