Treatment of CML Patients With Imatinib and Hydroxyurea
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 113
- 主要终点
- number of participants with complete molecular response as a measure of efficacy
研究概览
简要总结
The study will test the tolerability and efficacy of the combination therapy Imatinib/Hydroxyurea (HU) in patients with chronic myeloid leukemia (CML) in first chronic phase (CP1) newly diagnosted or failing interferon-based therapy.
详细描述
The protocol consists of a part 1, a phase I study that will enrol 20 patients, with the goal to determine the safety of the combination as well as the maximal tolerated dose. If the toxicity of the combination is acceptable, up to 200 more patients may be recruited and randomized to receive either Imatinib/HU or Imatinib alone (part 2).
Patients who meet the inclusion criteria will be started on 400 mg Imatinib daily. In part 1 of the protocol, the dose of HU will be increased by 500 mg at 3-weekly intervals until the maximal tolerated dose has been reached. In part 2 of the study, patients will be randomized to receive either the combination or Imatinib monotherapy.
Hematological and cytogenetic response will be evaluated at 3-months intervals during the first year, and at 6 months' intervals thereafter. Primary endpoints for part 1 are dose-limiting toxicity and maximal tolerated dose. Primary endpoints for part 2 are the rates of major and complete molecular response at 6, 12 and 18 months, respectively.
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
- •Ph-positive CML in CP1, newly diagnosed or resistant (hematologic or cytogenetic) or intolerant to interferon-based therapy
- •Age ≥ 18 years
- •Negative pregnancy test
- •Low- and intermediate risk patients younger than 45 with an HLA (Human Leukocyte Antigen) -matched sibling donor and medically fit to undergo allografting should be included only after they have been adequately counselled about the potential risk (of disease progression) associated with delaying the allograft
- •Informed consent
排除标准
- •Objective signs of disease progression beyond CP1 defined as
- •bone marrow or peripheral blood blasts > 15% and/or
- •blasts + promyelocytes ≥ 30% and/or
- •peripheral blood basophils ≥ 20% and/or
- •platelets < 100/nl and/or
- •chromosomal abnormalities in addition to the Ph chromosome
- •Findings suggestive of extramedullary involvement
- •Any severe and uncontrolled medical condition
- •Previous treatment with Imatinib (only part 2 of the study)
- •History of non-compliance
- •Simultaneous inclusion in other studies
- •Important note: previous treatment with Imatinib only is not an exclusion criterion for part 1 of the study.
研究组 & 干预措施
combination Imatinib + Hydroxyurea
Patients who meet the inclusion criteria will be started on 400 mg Imatinib daily. In part 1 of the protocol, the dose of HU will be increased by 500 mg at 3-weekly intervals until the maximal tolerated dose has been reached. In part 2 of the study, patients will be randomized to receive either the combination or Imatinib monotherapy.
干预措施: Imatinib (Drug)
combination Imatinib + Hydroxyurea
Patients who meet the inclusion criteria will be started on 400 mg Imatinib daily. In part 1 of the protocol, the dose of HU will be increased by 500 mg at 3-weekly intervals until the maximal tolerated dose has been reached. In part 2 of the study, patients will be randomized to receive either the combination or Imatinib monotherapy.
干预措施: Hydroxyurea (Drug)
monotherapy Imatinib
Imatinib monotherapy
干预措施: Imatinib (Drug)
结局指标
主要结局
number of participants with complete molecular response as a measure of efficacy
时间窗: 18 months
complete molecular response is achieved if BCR-ABL (breakpoint cluster region-Abelson murine leukemia) transcripts became undetectable
次要结局
未报告次要终点
研究者
Prof. Dr. med. Thoralf Lange
Prof. Dr. med. Thoralf Lange
University of Leipzig