Phase II Study of Individual 6-mercaptopurine(6MP) Dose Increments in Children With Acute Lymphoblastic Leukemia (ALL) Receiving High-dose Methotrexate (HDM) and PEG-asparaginase
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 3
- 主要终点
- Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported
研究概览
简要总结
The present pharmacokinetic (PK)-pharmacodynamic (PD) study will explore the toxicity and antileukemic response during the initial 3 months of individualised therapy of children and young adults with acute lymphoblastic leukemia (ALL). The investigators will on an individual toxicity-titrated basis attempt to increase the dose intensity of the 6-mercaptopurine used in the two-months post-remission treatment phase of lower risk childhood ALL. This will be performed together with continuous PEG-ASP (every 2nd week) and interspersed HD-MTX (5 g/m^2) every 3rd week. Thus, the trial will also test the feasibility of this particular drug combination.
详细描述
In addition to the details above we will also explore
- the relationship of the post-HD-MTX MRD-levels with the dose of 6MP, TPMT-activity, DNA-6TGN, E-6TGN, E-MeMP, E-MTX, and presence of ASP-antibodies,
- the early development of anti-ASP antibodies during continuous PEG-ASP therapy.
The study could improve the understanding of the pharmacodynamics of the 6MP/HD-MTX interaction in combination with PEG-ASP.
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
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •B-lineage ALL
- •1-17.9 years
- •WBC <100, clinical remission obtained day 2
- •Written consent to participation.
排除标准
- •Hypodiploidy
- •11q23-aberrations
- •TPMT-deficiency
- •Intolerance to MTX or 6MP
研究组 & 干预措施
6 mercaptopurine arm
All patients received basic daily 6MP (6-mercaptopurine) (25 mg/m^2) and in addition high-dose methotrexate(HDM) every 3rd week (3 times HDM in total) and PEG-asparaginase every 14th day. Patients increased the dose of 6MP 2 weeks after each HDM if if the myelotoxicity had been acceptable. This means 2 increments since the study stopped 2 weeks after the last HDM
干预措施: 6-mercaptopurine (Drug)
结局指标
主要结局
Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported
时间窗: 3 months ( 79 days )
Number of participants following the protocol treatment for the full consolidation therapy with toxicity in this pilot study trying to individually titrate 6-mercaptopurine to the highest tolerable level during Consolidation.
次要结局
- Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production(During the 3 months consolidation therapy)
研究者
Kjeld Schmiegelow
Professor
Rigshospitalet, Denmark