Measurable-residual Disease (MRD) Monitoring of Nucleophosmin 1 (NPM1)-Mutated Acute Myeloid Leukaemia (AML) and Pre-emptive Therapy With Oral Arsenic Trioxide-based Regimen
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Rate of NPM1 MRD negativity.
研究概览
简要总结
A prospective open-label phase 2 study will be designed to assess the efficacy of oral arsenic trioxide plus azacitidine in preventing relapses in patients with NPM1-mutant AML. After screening and eligibility assessment, patients will receive treatment with oral arsenic trioxide plus azacitidine for 12 months. The recruitment period will last for 24 months and it will take approximately 36 months for study completion.
详细描述
Eligible subjects with NPM1 MRD positivity will receive oral arsenic trioxide (oral-As2O3) (Arsenol ®) (5-10mg per day, from days 1-7 per cycle), ascorbic acid (1g per day, from days 1 - 7 per cycle) plus azacitidine (75mg/m2 per day subcutaneously, from days 1 to 3 per cycle). Each cycle of oral-As2O3 plus azacitidine will be given once every 28 days. The total duration of treatment is 12 months (12 cycles). Treatment will be day-care and outpatient based. Reduction in the dosage and duration of oral-As2O3 is required if the subject is experiencing adverse events (AEs). In case of grade 3 or above toxicity, the dosage of oral-As2O3 will be reduced to 5mg per day. Changes or interruption in dosages, their dates and time points will be recorded on the dosage administration record and the electronic case report form (eCRF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Adults ≥ 18 years
- •Diagnosis of AML with NPM1 mutation
- •Positive MRD for NPM1 mutation after completion of consolidation in transplant-ineligible patients
- •Positive MRD for NPM1 mutation after allogeneic HSCT
- •bilirubin ≤ 1.5 x upper limit normal (ULN); alanine aminotransferase (ALT) ≤ 2 x ULN or aspartate aminotransferase (AST) ≤ 2 x ULN; and prothrombin time versus control <3 seconds at screening
- •Glomerular filtration rate ≥ 50 mL/min (by MDRD equation or Cockcroft-Gault formula)
- •Corrected QT interval (QTc) (by Framingham formula) <500ms.
- •Able to give a written informed consent and fully comply to the requirements of the study.
排除标准
- •Patients on other investigational therapies
- •Prior exposure to azacitidine, decitabine or arsenic trioxide
- •Uncontrolled graft-versus-host disease (GVHD)
- •Eastern Cooperative Oncology Group (ECOG) performance status > 2
研究组 & 干预措施
Oral arsenic trioxide-Azacitidine
12 monthly cycles of oral arsenic trioxide (oral-As2O3) (Arsenol ®) (5-10mg per day, from days 1-7 per cycle), ascorbic acid (1g per day, from days 1 - 7 per cycle) plus azacitidine (75mg/m2 per day subcutaneously, from days 1 to 3 per cycle).
干预措施: Oral Arsenic Trioxide Formulation (Drug)
结局指标
主要结局
Rate of NPM1 MRD negativity.
时间窗: 36 months
This is defined as undetectable NPM1 mutant transcript with RQ-PCR on both the PB and BM following treatment, at a limit of detection of 10\^-5.
次要结局
- Duration of response(36 months)
- Safety of oral-As2O3 plus azacitidine, assessed using the common toxicity criteria for adverse events (CTCAE) version 5.0.(36 months)
- Leukaemia-free survival (LFS)(36 months)