A Phase I/II Multicenter Study of IY5511HCl in Philadelphia Chromosome Positive Chronic Myeloid Leukemia Patients Without Optimal Response or Tolerance to Bcr-Abl Tyrosine Kinase Inhibitors (Imatinib and/ or Dasatinib, Nilotinib)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 85
- 试验地点
- 2
- 主要终点
- Rate of Complete hematologic response(CHR)(Phase 2)
研究概览
简要总结
A Phase I/II multicenter study of IY5511HCl in Philadelphia chromosome positive chronic myeloid leukemia patients without optimal response or tolerance to Bcr-Abl tyrosine kinase inhibitors (Imatinib and/ or Dasatinib, Nilotinib) In this study, The efficacy and safety of CML patients who are resistant or intolerable to imatinib in the Chronic and Accelerated phases.
Phase 1
- To investigate the Maximum Tolerated Dose (MTD) and the Dose Limiting Toxicity (DLT) of oral Radotinib HCl bid (twice daily) in the Philadelphia chromosome-positive CML subjects who are resistant, suboptimal responsive, or intolerant to imatinib OR resistant or intolerant to at least one second-generation targeted anticancer agent while being resistant, suboptimal responsive, or intolerant to imatinib simultaneously.
Phase 2
- To investigate safety of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases.
- To evaluate hematologic and cytogenetic efficacy of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases.
详细描述
This study is a multi-center, open-label, Phase 1/2 clinical trial of Radotinib HCl, a targeted anticancer agent that inhibits the Bcr-Abl oncoprotein. It is aimed at determining the optimal therapeutic dose and confirming safety and efficacy of Radotinib HCl. Phase 1 study began at St. Mary's hospital in Korea and Phase 2 study is ongoing at 9 Korean sites and about 7 sites in China, India and Thailand will take part in Phase 2. After determination of a safe and proper therapeutic dose in Phase 1, Phase 2 began continuously to evaluate efficacy in chronic and accelerated phases. Before the start of the Phase 2 trial, interim or final reports for the Phase 1 trial were reviewed by the Korean Food and Drug Administration.
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
- •Age ≥ 18 years old
- •Ph+ CML patients who are resistant at chronic, accelerate, and acute phase, or suboptimal responsive, or intolerant to imatinib or resistant or intolerant to at least one second-generation targeted anticancer agent while being resistant, suboptimal responsive, or intolerant to imatinib simultaneously.
- •WHO Performance status of ≤2
- •Patients must have the following laboratory values With normal liver and renal function
- •Patients who have received interferon, other anti cancer drug or radiotherapy > 1 week prior to starting study drug.
- •Age ≥ 18 years old
- •Ph+ CML patients in chronic or accelerated phase who are resistant or intolerant to Imatinib mesylate
- •WHO Performance status of ≤2
- •Patients must have the following laboratory values With normal liver and renal function
- •Patients who have received interferon, other anti cancer drug or radiotherapy > 1 week prior to starting study drug.
排除标准
- •CNS infiltration
- •Impaired cardiac function, including any one of the followings.
- •LVEF <45% as determined by MUGA scan or echocardiogram
- •Clinically significant resting bradycardia
- •Severe GI disease that may cause drug absorption problem of study drug
- •Use of therapeutic Warfarin
- •Acute or chronic liver or renal disease
- •Other concurrent severe and/or uncontrolled medical conditions
- •Treatment with any hematopoietic colony-stimulating growth factors ≤1 week prior to starting study drug.
- •Patients who are currently receiving treatment with medications have the potential to prolong the QT interval
- •Patients who have received Imatinib, interferon, other anti cancer drug or chemotherapy ≤ 1 week
- •Patients who have received Nilotinib and Dasatinib ≤4 weeks prior to starting study drug.
- •Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- •Patients who are pregnant or breast-feeding or adults of reproductive potential not employing an effective method of birth control.
- •Patients not to agree using birth control during the study and for up 3 months following study completion.
- •HIV infection
- •Blast phase CML
- •CNS infiltration
- •Impaired cardiac function, including any one of the following
- •LVEF< 45% as determined by MUGA scan or echocardiogram
- •Use of Cardiac pacemaker
- •ST depression > 1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads
- •Congenital long QT syndrome
- •History of, or presence of significant ventricular or atrial tachyarrhythmias
- •Clinically significant resting bradycardia
- •QTcF> 480 msec on screening ECG
- •Right bundle branch block + left anterior hemiblock, Bifascicular block
- •Angina pectoris
- •Severe GI disease that may cause drug absorption problem of study
- •Use of therapeutic Warfarin
- •Acute or chronic liver or renal disease
- •Other concurrent severe and/or uncontrolled medical conditions
- •Treatment with any hematopoietic colony-stimulating growth factors ≤1 week prior to starting study drug.
- •Patients who are currently receiving treatment with medications have the potential to prolong the QT interval
- •Patients who have received Imatinib, interferon, other anti cancer drug or chemotherapy ≤ 1 week
- •Patients who have received wide field radiotherapy ≤4 weeks prior to starting study drug.
- •Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- •Patients who are pregnant or breast-feeding or adults of reproductive potential not employing an effective method of birth control
研究组 & 干预措施
Radotinib
Phase 1 : 200mg/kg or 1200mg/m^2
Phase 2 : 400mg Bid
干预措施: Radotinib (Drug)
结局指标
主要结局
Rate of Complete hematologic response(CHR)(Phase 2)
时间窗: 12 months
Main parameters for response assessment in the chronic and accelerated phases include Major Hematologic Responses (MR; No Evidence of Leukemia or NEL + Complete Hematologic Response or CHR) lasting for 4 weeks and at least one major cytogenetic response (MCyR)
To investigate the Maximum Tolerated Dose(Phase 1)
时间窗: 12 month
Radotinib will be given orally twice daily. Dose will be increased until it reaches MTD or the blood concentration of Radotinib stops rising
次要结局
- To investigate the Dose Limiting Toxicity(Phase 1)(12 months)
- Rate of complete Cytogenetic Response(CCyR)(Phase 2)(12 months)
- Adverse events(Phase 1& Phase 2)(12 months)
- Progression-free survival or PFS(12 months)