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 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 1. To investigate safety of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases. 2. 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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
85
50mg, 100mg or 200mg Capsule BID
Local institution
Mumbai, Maharashtra, India
Local institution
Mumbai, Mazagaon, India
Local institution
Daegu, Buk-gu, South Korea
Local institution
Jeonju, Deokjin-gu, South Korea
Local institution
Ulsan, Dong-gu, South Korea
Local institution
Anyang-si, Dongan-gu, South Korea
Local institution
Hwasun, Hwasun-eup, South Korea
Local institution
Seoul, Jongro-ku, South Korea
Local institution
Busan, Seo-gu, South Korea
Seoul St. Mary's hospital
Seoul, Seocho-gu, South Korea
...and 2 more locations
To investigate the Maximum Tolerated Dose(Phase 1)
Radotinib will be given orally twice daily. Dose will be increased until it reaches MTD or the blood concentration of Radotinib stops rising
Time frame: 12 month
Rate of Complete hematologic response(CHR)(Phase 2)
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)
Time frame: 12 months
To investigate the Dose Limiting Toxicity(Phase 1)
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.
Time frame: 12 months
Rate of complete Cytogenetic Response(CCyR)(Phase 2)
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.
Time frame: 12 months
Adverse events(Phase 1& Phase 2)
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.
Time frame: 12 months
Progression-free survival or PFS
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.
Time frame: 12 months
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