Persistence Of Major Molecular Remission In Chronic Myeloid Leukemia After A Second Stop Of Tki Treatment In Patients Who Failed An Initial Stop Attempt: A Multicenter Prospective Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 134
- 试验地点
- 20
- 主要终点
- successful MMR maintenance
研究概览
简要总结
This study will enroll CML patients who have failed a first TKI stopping attempt. After failure and at least a year of TKI treatment, patients will proceed to dasatinib treatment for another 2 years. If MR4 or better is re-achieved and maintained for at least one year, patients will be eligible for a second stop. After verification of MR4, TKI treatment will be stopped and patients followed in the same manner as after first stop. If MMR is lost (BCR-ABL >0.1% (IS)), TKI treatment will once again be restarted.
详细描述
The DASTOP2 study aims to retreat patients who relapse in the Euro-SKI study (or who stopped TKI treatment outside trials but according to EURO-SKI procedures), with TKI for at least another 3 years, out of last two years with dasatinib. If MR4 or better is re-achieved and maintained for at least one year, patients will be eligible for a second stop. After verification of MR4, TKI treatment will be stopped and patients followed in the same manner as after first stop. If MMR is lost (BCR-ABL >0.1% (IS)), TKI treatment will once again be restarted.
Patients exhibiting hematological relapse after first stop attempt will not be offered a second stop within this study. The same applies to patients in whom TKI was restarted prematurely (without loss of MMR).
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 chronical phase (CP) under TKI treatment after failing a prior attempt to stop treatment within EURO-SKI or outside the study but according to EURO-SKI trial procedures. For the latter group this requires at least 3 years of TKI treatment (first line or second line due to intolerance to first line) before first stop, and MR4 for at least one year before stopping.
- •Treated with TKI for at least one year after having failed a prior attempt to stop TKI. Previous TKI can be any.
- •Typical BCR/ABL1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis or later during the disease course.
- •18 years or older.
排除标准
- •Previous hematological relapse after first stop of TKI.
- •Previous AP/BC at any time in the history of the disease.
- •Restart of TKI without loss of MMR after first stop
- •Current participation in another clinical study.
- •Previous or planned allogeneic stem cell transplantation.
- •Patients with contra-indications to dasatinib therapy due to comorbidities.
- •Subjects with acute hepatitis B virus (HBV) infections.
- •Uncontrolled or significant cardiovascular disease.
- •Pulmonary arterial hypertension.
- •Pleural or pericardial effusions of any grade at study entry are excluded
- •History of significant bleeding disorder unrelated to CML
- •Hypersensitivity to dasatinib and excipients of dasatinib tablets.
研究组 & 干预措施
dasatinib
2 years of dasatinib treatment before discontinuation if MR 4 is achieved for at least 1 year
干预措施: Dasatinib (Drug)
结局指标
主要结局
successful MMR maintenance
时间窗: one year
The proportion of patients maintaining MMR at 12 months after discontinuing TKI a second time (survival without loss of major molecular response, MMR, defined as BCR-ABL1 \> 0.1% on IS at one time point).
次要结局
- correlates with succesful stop(1 year)
- reachievement of MR4(1 year)
- Time to reachievement of MR4(1 year)
- Adverse events after TKI withdrawal(1 year)
- Overall survival(1 year)
- Progression-free survival(1 year)
- TKI restart without prior molecular relapse(1 year)
研究者
J.J.W.M. Janssen
Clinical Hematologist, Deputy Chief of Department of Hematology
Amsterdam UMC, location VUmc