Venetoclax Combined With Azacitidine Plus Homoharringtonine Versus Venetoclax Combined With Azacitidine for Relapsed/Refractory Acute Myeloid Leukemia：an Open-label, Multicentre, Randomised Phase 3 Trial
试验速览
- 阶段
- 3 期
- 入组人数
- 162
- 试验地点
- 1
- 主要终点
- Overall response rate
研究概览
简要总结
This is a prospective, multi-center, phase 3 randomized controlled clinical study comparing VAH and VA regimens for the salvage treatment of the patients with relapsed/refractory AML. Approximately 164 subjects will be randomized in a 1:1 ratio to receive VAH regimen (82 subjects) or VA regimen (82 subjects) for salvage therapy. Randomization is done with permuted blocks (block size four), and implemented through an interactive web-based response system.
VAH regimen: VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.
VA regimen: The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.
The primary endpoint was overall response rate (ORR) after 2 cycles of trial therapy.
The secondary endpoints were CRc after 2 cycles of trial therapy, overall survival (OS), event-free survival (EFS) and relapse at 2 year, and safety.
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 relapsed/refractory AML The diagnosis of AML or relapsed AML was based on the criteria from NCCN, defined as recurrence of blasts in the peripheral blood (PB) or bone marrow (BM) blasts > 5% or development of extramedullary disease of patients after achieving a CR. Refractory AML was defined as no composite complete remission (CRc) and a reduction in bone marrow blasts of less than 50% after one cycle or no CRc after two cycles.
- •Age 18 to 65 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Sign informed consent form, have the ability to comply with study and follow-up procedures
排除标准
- •Acute promyelocytic leukemia (AML subtype M3)
- •Previous exposure to the treatment of VEN-based regimen
- •Life expectancy less than 30 days after salvage therapy
- •Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
- •Respiratory failure ( PaO2 ≤60mmHg)
- •Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal [ULN], alanine aminotransferase or aspartate aminotransferase ≥2 times the ULN)
- •Renal dysfunction (creatinine ≥2 times the ULN or creatinine clearance rate < 30 mL/min)
- •ECOG performance status 3, 4 or 5
- •With any conditions not suitable for the trial (investigators' decision)
- •Active acute or chronic graft-versus-host disease (GVHD). Active acute GVHD or chronic GVHD was defined as GVHD requiring either at least 1 mg/kg per day of prednisone (or equivalent) or treatment beyond systemic corticosteroids.
- •Patients with pregnancy
研究组 & 干预措施
VAH regimen
VEN begins at 100 mg on day 1 and increases stepwise over 3 days to reach the target dose of 400 mg (100 mg, 200 mg, 400 mg); dosing is continued at 400 mg per day from day 4 through day 14; azacitidine (75 mg/m²) is administered subcutaneously on days 1-7, and HHT (1 mg/m²) on days 1-7.
干预措施: VEN combined with azacitidine plus homoharringtonine (Drug)
VA regimen
The use of VEN is just the same as it dose in VAH regimen except lasting for 28 days. The use of azacitidine is exactly the same as VAH group does.
干预措施: VEN combined with azacitidine (Drug)
结局指标
主要结局
Overall response rate
时间窗: At the end of Cycle 2 (each cycle is 28 days)
Overall response including CR/CRi and PR
次要结局
- Composite complete remission rate(At the end of Cycle 2 (each cycle is 28 days))
- Overall survival(From date of randomization until date of death from any cause, assessed up to 12 months.)
- Event-free survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months)
- Relapse(1 year)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Baseline to 30 day post the salvage therapy)
研究者
Qifa Liu
Department director
Nanfang Hospital, Southern Medical University