Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome and Chronic Myeloid Leukemia Chronic Phase Patients

Study Overview
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Brief Summary
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In this study, the efficacy and safety of two radotinib doses, 300 mg twice daily and 400 mg twice daily, will be compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

Official Title
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A Phase 3 Multinational, Multi-center, Open-Label, Randomized Study of the Efficacy of Radotinib Versus Imatinib in Newly Diagnosed Ph+ CML Patients in Early Chronic Phase

Conditions
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Leukemia, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Philadelphia Chromosome, Bone Marrow Diseases, Hematologic Diseases

Intervention / Treatment
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* Drug: Imatinib
* Drug: Radotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with confirmed diagnosis of chronic phase CML within last 3 months Patients with cytogenetically confirmed Ph positive CML in early chronic phase Exclusion Criteria: Patients with Philadelphia chromosome negative but BCR-ABL positive CML Patients who used imatinib for 8 days or longer before study entry Patients who had been treated with other targeted anti-cancer therapy, except for Hydrea or Agrylin, which inhibits the growth of leukemic cells Patients with impaired cardiac function Cytologically confirmed CNS involvement Severe or uncontrolled chronic medical condition Other significant congenital or acquired bleeding disorders that are not related to underlying leukemia Patients who had a major surgery within 4 weeks prior to study entry or has not recovered from side effects of such surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imatinib<br>Imatinib 400mg QD | Drug: Imatinib<br>* 400mg/Tab, QD<br>* Other names: Gleevec;|
| Experimental: Radotinib 600mg<br>Radotinib 300mg BID | Drug: Radotinib<br>* 100mg or 200mg/Capsule, 300mg or 400mg BID<br>* Other names: IY5511HCl;|
| Experimental: Radotinib 800mg<br>Radotinib 400mg BID | Drug: Radotinib<br>* 100mg or 200mg/Capsule, 300mg or 400mg BID<br>* Other names: IY5511HCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Major Molecular Response(MMR) by 12 months | Rate of Major Molecular Response (MMR) at Any Time within 12 months. MMR by 12 months will be assessed as responder if the patient has response at any time within 12 months. A major molecular response rate is defined as the ratio (%) of BCR-ABL/ABL ≤ 0.1% by international scale or a 3-log reduction in BCR-ABL transcript level from standardized baseline, as measured by standardized RQ-PCR assay. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete cytogenetic response (CCyR) by 12 months | Complete cytogenetic response is defined as complete disappearance of Philadelphia-positive in at least 20 metaphases examined. Chromosome analysis performed on less than 20 metaphases will not be accepted for this study | 12 months | 
| Rate of complete molecular response (CMR) by 12 months | Complete molecular response is defined as negative BCR-ABL transcript levels, as measured twice by the internationally standardized RQ-PCR assay. The rate of complete molecular response by cycle 12 is defined as an at least 4.5 log reduction in BCR-ABL transcript levels from standardized baseline or BCR-ABL/ABL % ≤ 0.005% by the international scale. | 12 months | 
| Rate of major molecular response (MMR) at 12 months | Rate of Major Molecular response will be assessed at 12 months at that timepoint. Number of Participants With Major Molecular Response (MMR) at 12 months. | 12 month | 
| Rate of subjects with disease progression | Disease progression by month 12 will be compared between each groups. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radotinib, CML-CP, Chronic Myeloid Leukemia, chronic phase