Imatinib Continuation Versus Nilotinib 300 mg Twice Daily in Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase and Major Molecular Re-sponse (MMR) Without Molecular Response ≥ 4.5 Log (MR4.5) Receiving Imatinib at a Dose of 400 to 800 mg Daily. An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 14
- 试验地点
- 18
- 主要终点
- Proportion of patients with confirmed MR4 after two years of study treatment
研究概览
简要总结
This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5
详细描述
This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5 (after having received Imatinib 400 to 800 mg daily for at least 18 months) to determine the proportion of patients with confirmed MR4 after two years. Patients in treatment arm A (Imatinib) who do not achieve confirmed MR4 2 years after randomisation will be offered cross-over from Imatinib 400 to 800 mg daily to Nilotinib 300 mg twice daily. One hundred thirty-two (132) patients will be included and randomised 1:1 to each treatment arm.
The study will be stratified by duration of Imatinib treatment before screen-ing (≤36 months / >36 months) as well as by the level of response at inclusion (MMR / MR4).
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
- 未提供
排除标准
- •Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha
- •Evidence of features of accelerated or blast phase at any time
- •Previous loss of hematologic or cytogenetic response
- •Concomitant medications known to be strong inducers or inhibitors of P450 Isoenzyme CYP3A4
- •Finding of a secondary BCR-ABL resistance mutation at any time
- •History of intolerance to Imatinib that required treatment interruption longer than 4 weeks (cumulative) or dose reductions to less than 400 mg daily for longer than 4 weeks (cumulative) during the last 12 months before informed consent
- •Patients who had prior allogeneic, syngeneic, or autologous bone mar-row transplant or stem cell transplant
- •Patients unwilling to or unable to comply with the planned therapeutic intervention or to comply with the study treatment visits including blood sample collection within the protocol
- •History of pancreatitis, chronic inflammatory diseases or autoimmune diseases
- •Patients who underwent solid organ transplantation
- •Impaired cardiac function, including any of the following:
- •History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemi block, bifascicular block in screening ECG
- •Use of a cardiac pacemaker
- •ST depression of > 1mm in 2 or more leads and/or T wave inver-sions in 2 or more contiguous leads in screening ECG
- •Congenital Long QT Syndrome
- •QTc> 450 msec in the screening ECG
- •QT prolonging concomitant medication
- •History of or presence of significant ventricular or atrial tachy-arrhythmia in screening ECG
- •History of or presence of clinically significant resting bradycardia (< 50 beats per minute)
- •Myocardial infarction within 12 months prior to informed consent
- •Unstable angina diagnosed or treated during the past 12 months before informed consent
- •Other clinically significant heart disease (e.g., congestive heart fail-ure, uncontrolled hypertension, history of labile hypertension)
- •Known HIV and/or hepatitis B or C infection (testing is not mandatory)
- •Other malignancies within the past 3 years before informed consent except for adequately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin
- •Women who are pregnant or breast feeding
- •Male/female patients of reproductive potential unwilling to practice a highly effective method of birth control
- •History of noncompliance to medical regimens
- •Treatment with another investigational product during this study or during the last 30 days prior to informed consent
研究组 & 干预措施
Imatinib
Imatinib 400-800mg, daily, maximum 6 years
干预措施: Imatinib (Drug)
Nilotinib
Nilotinib, 300mg, twice daily, maximum 6 years
干预措施: Nilotinib (Drug)
结局指标
主要结局
Proportion of patients with confirmed MR4 after two years of study treatment
时间窗: 2 years
Proportion of patients with confirmed MR4 at two years of study treatment in both treatment arms. Confirmed MR4 at two years is defined as either BCR-ABL ≤ 0.01% IS at 21 and 24 months or BCR-ABL ≤ 0.01% IS at 24 months and confirmation within six weeks
次要结局
未报告次要终点
研究者
Prof. Dr. Nikolas von Bubnoff
Mr.
University Hospital Freiburg