Prospective Non-randomized Stratified Study of REduction And DIscontinuation Treatment of TKI (Imatinib, Nilotinib, Dasatinib and Bosutinib) in Adults With Ph+ Chronic Myeloid Leukemia With Stable Deep Molecular Response
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Overall survival, survival without molecular relapse
研究概览
简要总结
The main goal of this study is to evaluate the stability of molecular response (major and deep molecular response( MMR and DMR)) in patients with chronic myeloid leukemia (CML) with stable DMR after two-stage dose reduction phase and discontinuation treatment TKI: imatinib, nilotinib, dasatinib and bosutinib.
详细描述
The duration of the dose reduction phase will be 12 months. This phase will have two stage of 6 months, respectively.
The dose of imatinib, nilotinib, dasatinib or bosutinib will be reduced by 25-50% on the first stage, and by another 25% on the second stage.
- The initial dose of imatinib will be 400 mg daily. The dose will be reduced by 300 mg daily on the first stage, by 200 mg daily - on the second stage.
- The initial dose of nilotinib will be 300 or 400 mg twice daily. The dose will be reduced by 400 mg daily on the first stage, by 200 mg daily - on the second stage.
- The initial dose of dasatinib will be 100 or 140 mg daily. The dose will be reduced by 50 mg daily on the first stage, by 25 mg daily - on the second stage.
- The initial dose of bosutinib will be 500 mg daily. The dose will be reduced by 300 mg daily on the first stage, by 200 mg daily - on the second stage.
All patients with stable deep molecular response (at least 2 years) will be included in treatment free remission phase (TFR-phase). The duration of TFR-phase will be 24 months.
The CML patients can enter the study already on reduced doses TKI, if they will meet the inclusion criteria.
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
- •CML in chronic phase.
- •TKI treatment for at least 3 years.
- •DMR (BCR-ABL≤0.01%) for at least 1 year, MMR (BCR-ABL≤0.1%) for at least 2 years
- •At least 3 molecular results over the preceding 24 months, which confirm the presence of MMR and DMR
- •Written Informed Consent
- •CML patients with DMR for at least 1 years and MMR for at least 2 years after STOP TKI in anamnesis.
- •For patients who are on the reduced dose TKI (1 stage) at the time of inclusion in the study
- •The duration of therapy at reduced doses of TKI phase I is at least 6 months.
- •For patients on the reduced dose TKI (2 stage, before TFR phase) at the time of inclusion in the study
- •DMR (BCR-ABL≤0.01%) for at least 2 years
- •The duration of therapy at reduced doses of TKI phase 1 is for at least 6 months, the total duration of therapy at reduced doses is for at least 12 months.
排除标准
- •Age under 18
- •CML in accelerated phase or blast crisis at any time
- •Lack of Written Informed Consent
- •Pregnant or lactating women
研究组 & 干预措施
The TKI dose reduction
Imatinib, nilotinib, dasatinib or bosutinib; the two stage of TKI dose reduction phase for 12 months (6 months and 6 months, respectively).
干预措施: Imatinib (Drug)
The TKI dose reduction
Imatinib, nilotinib, dasatinib or bosutinib; the two stage of TKI dose reduction phase for 12 months (6 months and 6 months, respectively).
干预措施: Nilotinib (Drug)
The TKI dose reduction
Imatinib, nilotinib, dasatinib or bosutinib; the two stage of TKI dose reduction phase for 12 months (6 months and 6 months, respectively).
干预措施: Dasatinib (Drug)
The TKI dose reduction
Imatinib, nilotinib, dasatinib or bosutinib; the two stage of TKI dose reduction phase for 12 months (6 months and 6 months, respectively).
干预措施: Bosutinib (Drug)
结局指标
主要结局
Overall survival, survival without molecular relapse
时间窗: 37 months
次要结局
- The proportion of patients with molecular relapse who achieved MMR and DMR after the resumption TKI therapy in standard doses(37 months)
- Clinical factors, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.(37 months)
- Biological factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.(37 months)
- The proportion of patients who resolved the adverse events after TKI dose reduction and discontinuation of TKI therapy(37 months)
- The proportion of patients who have TKI withdrawal syndrome after TKI dose reduction and discontinuation of TKI therapy.(37 months)
- Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.(37 months)