Philadelphia Chromosome Positive CML Patients Without Optimal Response or Tolerance to Bcr-Abl TKI
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.
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.
- 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.
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- To investigate the Maximum Tolerated Dose(Phase 1) [ Time Frame: 12 month ] [ Designated as safety issue: No ]Radotinib will be given orally twice daily. Dose will be increased until it reaches MTD or the blood concentration of Radotinib stops rising
- Rate of Complete hematologic response(CHR)(Phase 2) [ Time Frame: 12 months ] [ Designated as safety issue: No ]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 Dose Limiting Toxicity(Phase 1) [ Time Frame: 12 months ] [ Designated as safety issue: No ]The initial cohort will include 3 subjects who will receive 100mg Radotinib daily. If DLT is observed in one of the 3 subjects, the same dose will be given to 3 more subjects to evaluate safety.
- Rate of complete Cytogenetic Response(CCyR)(Phase 2) [ Time Frame: 12 months ] [ Designated as safety issue: No ]Cytogenetic response rate will be calculated as the percentage of Ph+ bone marrow metaphases as follows at least 20 bone marrow metaphases should be analyzed.
- Adverse events(Phase 1& Phase 2) [ Time Frame: 12 months ] [ Designated as safety issue: No ]All adverse events recorded during the study will be itemized and summarized. Severity, relation to the study medication, and seriousness will be summarized for each adverse event.
- Progression-free survival or PFS [ Time Frame: 12 months ] [ Designated as safety issue: No ]It is defined as the duration from the first day of administration to the earliest day of disease progression or death for certain causes. In subjects who have shown response, disease progression is defined as loss of MCyR.
|Study Start Date:||July 2008|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Phase 1 : 200mg/kg or 1200mg/m^2
Phase 2 : 400mg Bid
50mg, 100mg or 200mg Capsule BID
Other Name: IY5511HCl
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.
|Mumbai, Maharashtra, India, 741-234|
|Mumbai, Mazagaon, India, 512-364|
|Korea, Republic of|
|Daegu, Buk-gu, Korea, Republic of, 511-230|
|Jeonju-si, Deokjin-gu, Korea, Republic of, 212-789|
|Ulsan, Dong-gu, Korea, Republic of, 411-978|
|Anyang-si, Dongan-gu, Korea, Republic of, 751-231|
|Chonnam, Hwasun-Gun, Korea, Republic of, 322-511|
|Seoul, Jongro-ku, Korea, Republic of, 231-855|
|Busan, Seo-gu, Korea, Republic of, 400-321|
|Seoul St. Mary's hospital|
|Seoul, Seocho-gu, Korea, Republic of|
|Suwon, Yeongtong-gu, Korea, Republic of, 781-512|
|Bangkok, Phyathai, Thailand, 215-714|
|Study Director:||IL-yang Pharm||IL-YANG Pharmaceutical.Co.,Ltd.|