A Phase II Randomized, Multicenter Study of Treatment-free Remission in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Patients Who Achieve and Sustain MR4.5 After Switching to Nilotinib
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 54
- 主要终点
- Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase
研究概览
简要总结
To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5
详细描述
Study protocol included criteria for study termination that was met when > 2 patients lost CCyR during TFR phase (> 1% BCR-ABL); This study was terminated early as > 2 cases of confirmed loss of complete cytogenetic response were reported despite BCR-ABL monitoring during the TFR Phase. All cases achieved MR4.5 after Nilotinib treatment re-initiation and maintained until end of study; trial did not mandate re-initiation within 4 weeks after loss of MMR_ that was a requirement in other Nilotinib TFR trials Initial sample size was 300 patients with CML-CP; Amendment #2 in June 2015 reduced sample size to 59 due to recruitment challenges; Study endpoint analysis and interpretations of data were challenging due to small sample size for early study closure..
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
- •diagnosis of CML
- •Treated with at least 1 year of imatinib
- •Bcr-Abl level by PCR must be less than or equal to 0.1% and greater than 0.0032% by PCR reported on the International scale confirmed during screening
- •Written informed consent obtained prior to any screening procedures performed
排除标准
- •T315I mutation
- •Prior imatinib failure or had accelerated phase or blast crisis CML
- •Impaired cardiac function
- •Pregnant or lactating women
研究组 & 干预措施
Treatment Free Remission
Patients entered a monitoring phase for 2 years and received 300 mg nilotinib mg bid. Patients who achieved MR4.5 entered a Consolidation Phase and were treated with nilotinib for 2 years. If MR4.5 was sustained during the Consolidation phase, patients were eligible to stop taking niltoinib during the treatment-free remission (TFR) phase.
干预措施: nilotinib (Drug)
结局指标
主要结局
Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase
时间窗: 6 months after stopping nilotinib therapy
Percentage of particpants without confirmed loss of MMR within 6 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, in the first 6 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase. Molecular relapse is defined as having a confirmed BCR-ABL ratio above MMR (2 consecutive BCR-ABL levels \>0.1% IS taken approximately 4 weeks apart).
次要结局
- Relapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5).(7 years)
- Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase(12 and 24 months after starting the TFR)
- Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse(Restart of nilotinib up to month 6, 12 and 24)
- Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause.(Baseline up to approximately 5 years)
- Overall Survival (OS)(Baseline up to approximately 5 years)
- Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment(From baseline to time to when MR4.5 is confirmed, up to 24 months, and from end of Consolidation Phase to 6 and 12 months into the TFR Phase)
- Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set(From baseline to time to when MR4.5, up to 24 months, is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase)
- Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set(From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase)
- Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set(At month 3 in Consolidation Phase)
- Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set(Month 12 in Consolidation Phase)
- Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set(Month 24 in Consolidation Phase)
- Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set(Month 6 in in Treatment Free Remission Phase)
- Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set(Month 12 in in Treatment Free Remission Phase)