A PROSPECTIVE RANDOMIZED PHASE II STUDY EVALUATING THE OPTIMIZATION OF THE RESIDUAL PLASMATIC LEVEL OF DASATINIB (SPRYCEL®) 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
- 289
- 试验地点
- 42
- 主要终点
- Cumulative rate of significant AE
研究概览
简要总结
This protocol is a multicentric interventional phase II study from the French CML Intergroup (FILMC).
The core of the protocol is to explore the efficacy and safety of an optimization strategy consisting in the modulation of the dasatinib daily dose according to the results of repeated plasmatic levels of dasatinib.
The objective of this strategy is to improve the overall results of the treatment of early CP-CML in order to avoid the development of resistance and BCR-ABL tyrosine kinase mutations.
The study will be conducted in selected FILMC and Canadian centers.
The study is sponsored by the Hôpitaux de Versailles and supported by Bristol-Myers Squibb. The dasatinib treatment will be provided by Bristol-Myers Squibb until marketing authorization is granted in that indication.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patient ≥ 18 years
- •ECOG Performance Status score 0-2
- •Philadelphia chromosome positive newly diagnosed (≤ 3 months) CP-CML
- •patients not previously treated except with hydroxyurea or imatinib (less than 4 weeks for imatinib)
- •Signed written inform consent
- •Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional ULN; ALT and AST ≤ 2.5 times the institutional upper limit of normal (ULN).
- •Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN.
- •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 a tyrosine kinase inhibitor (TKI) except with imatinib during less than 4 weeks.
- •Active malignancy
- •Uncontrolled or significant cardiovascular disease
- •Patients with QTc > 450 ms
- •Significant bleeding disorder unrelated to CML
- •Concurrent severe diseases which exclude the administration of therapy
研究组 & 干预措施
B
Arm B : Dasatinib standard dose with Cmin < 3nM analysed on blood after 7-10 days dasatinib 100mg intake
干预措施: Dasatinib (Drug)
A1
Arm A1: Dasatinib dose adjustment based on Cmin ≥3nM value analysed on blood after 7-10 days dasatinib 100mg intake
干预措施: Dasatinib (Drug)
A2
Arm A2: Dasatinib standard dose (100mg/d) with Cmin ≥ 3nM analysed on blood after 7-10 days dasatinib 100mg intake
干预措施: Dasatinib (Drug)
结局指标
主要结局
Cumulative rate of significant AE
时间窗: 12 months therapy
The cumulative rate of serious AEs defined by grade 3-4 fluid retention, all grade pleural effusion, haematological grade 3-4 AEs related to dasatinib and/or all AE leading to dasatinib discontinuation within the first year of therapy
次要结局
- Cumulative duration of dasatinib interruption(12 months therapy)
- Mean dose of dasatinib(12 months therapy)
- Cumulative rate of complete cytogenetic response(12 months therapy)
- Cumulative rate of major molecular response(12 months therapy)
- Median dose of dasatinib administered(12 months therapy)
- Cumulative rate of complete molecular response(12 months therapy)
- Time to molecular response(12 months therapy)
- Relationship between peak plasmatic level and efficacy(12 months therapy)
- Relationship between through plasmatic level and efficacy(12 months therapy)
- Progression-free survival at 5 years(12 months therapy)
- Overall survival at 5 years(12 months therapy)
- Lymphocyte populations before and during dasatinib therapy(12 months therapy)
- Rate of sustained major molecular remission after dasatinib discontinuation in patients in complete molecular response(12 months therapy)
- Rate of treatment interruptions(12 months therapy)
研究者
Philippe ROUSSELOT
Clinical Coordinator
Versailles Hospital