A Prospective Randomized Phase II Study Evaluating the Monitoring of Imatinib Mesylate (Glivec®) Plasmatic Through Level in Patients Newly Diagnosed With Chronic Phase Chronic Myelogenous Leukaemia (CP-CML).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 139
- 试验地点
- 20
- 主要终点
- The major molecular response rate at 12 months in cohort 1.
研究概览
简要总结
Imatinib mesylate (Gleevec/Glivec, IM) is currently the gold standard or CML-CP front line therapy. The recommended dose of IM is 400 mg/day. The rates of complete cytogenetic responses at 3, 6 and 12 months are 27%, 50% and 69% respectively. The optimal IM daily dose is not yet determined and randomized studies addressing this question are on-going. First results from the TOPS trial (EHA 2008 congress) suggest a more rapid kinetic of response for patients treated with imatinib high dose. Recent studies revealed that initial Imatinib plasmatic dosage is predictive for achieving complete cytogenetic responses (CCR) and that a dosage of 1000 ng/ml is associated with a higher proportion of major molecular responses (MMR) (Picard et al., Blood 2007, Larson et al. Blood 2007).
Results from the study of Larson et al. indicate that around 40% of the patients had a trough plasmatic level below 1000 ng/ml after day 28 of imatinib 400 mg/d. The major molecular response rate at 12 months for the patients with the lower plasmatic through level is 25.4% compared to 40.1% for the patients with a plasmatic dosage over 800 to 1000 ng/ml.
Investigators propose to adapt the imatinib daily dose in case of imatinib through plasmatic level at day 28 below 1000 ng/ml. Patients with a trough plasmatic dosage ≤ 1000 ng/ml will be randomized between a prospective adaptation strategy of the imatinib daily dose (cohort 1) versus observation only (cohort 2). The patients with adequate imatinib dosage (> 1000 ng/ml) will be followed up according the ELN recommendation (cohort 3). Imatinib trough plasmatic level will then be rechecked every month thereafter for patients in cohort 1 and cohort 2 and every three months in cohort 3. The first endpoint of the study will be the rate of major molecular response at 12 months in cohort 1. Our hypothesis is to improve the 12 months MMR rate with the optimized strategy (cohort 1) from 25% of MMR at 12 months to 40% of MMR at 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Male or female patient ≥ 18 years
- •Philadelphia chromosome positive newly diagnosed chronic myelogenous leukaemia (≤ 4 months) in first chronic phase.
- •Not previously treated with tyrosine kinase inhibitors other than imatinib
- •Prior treatment with imatinib during less than 13 weeks
- •Signed written inform consent
- •Women of childbearing potential (WOCBP) must be using an adequate method of contraception
排除标准
- •Patients with BCR-ABL positive, Philadelphia negative CML
- •Patient previously treated with TKI other than imatinib
- •Active malignancy
- •Concurrent severe diseases which exclude the administration of therapy
研究组 & 干预措施
Active comparator
Cohort 2 : Imatinib standard dose Imatinib through dosage < 1000 ng/ml
干预措施: active comparator (Other)
Experimental arm
Cohort 1 : dose adjustment based on trough plasmatic level value Imatinib through dosage < 1000 ng/ml
干预措施: Posology dose modification (Drug)
结局指标
主要结局
The major molecular response rate at 12 months in cohort 1.
时间窗: 12 months
次要结局
- Progression free survival(5 years)
- Event free survival(5 years)
- Overall survival(5 years)
- Complete cytogenetic response at 6 and 12 months(12 months)
- Major molecular response rate at 12 months in cohort 2 and cohort 3.(12 months)
- Major molecular response at 3, 6, and 9 months(9 months)
- Complete molecular response 6 and 12 months(12 months)
- Relationship between plasmatic dosage and efficacy(12 months)
- Relationship between plasmatic dosage and tolerance(12 months)
研究者
Philippe ROUSSELOT
Study coordonator
Versailles Hospital