Randomized Evaluation of Radotinib Versus Imatinib in Phase III Study for Efficacy With Chinese Patients (RERISE China)

Study Overview
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Brief Summary
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This is a Phase III, multi-center, open-label, parallel, 2-arm, randomized study to evaluate the efficacy and safety of radotinib 300 mg Bis In Die(BID) versus imatinib 400 mg Quaque Die(QD). This study will be conducted in Chinese patients with newly diagnosed Ph+ Chronic Myelogenous Leukemia(CML)-Chronic Phase(CP) who are previously untreated for Chronic Myelogenous Leukemia(CML).

Detailed Description
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Patients randomized to the radotinib arms will receive 300 mg of radotinib BID at approximately 12-hour intervals. Patients randomized to the imatinib 400 mg arm will receive imatinib once a day throughout the study. The primary efficacy endpoint is the rate of Major Molecular Response(MMR) at 12 months (1 month = 4 weeks = 28 days), defined as BCR ABL1/ABL% ≤ 0.1% by international scale. The Molecular Response(MR) rate will be measured every 3 months by Real-time Quantitative(RQ)-Polymerase Chain Reaction(PCR) in a central laboratory. All patients will be treated and/or followed for 12 months (48 weeks) after randomization.

Official Title
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A Phase III, Multi-center, Open-Label, Randomized Study of the Efficacy of Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Chinese Patients in Chronic Phase

Conditions
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Chronic Myeloid Leukemia, Chronic Phase

Intervention / Treatment
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* Drug: Radotinib
* Drug: Imatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: China who are 18 years of age or older. Eastern cooperative oncology group (ECOG) score 0, 1, or 2. Patients with confirmed diagnosis of CML-CP within last 6 months. Patients with cytogenetically confirmed Ph+ CML in chronic phase Patients with typical BCR-ABL1 transcript type such as b2a2 and b3a2. Patients with adequate organ function. Women of childbearing potential should have negative serum or urine pregnancy test within 14 days before study entry. Patients providing written informed consent before initiation of any study-related activities. Exclusion Criteria: Patients with Philadelphia chromosome negative but BCR-ABL1 positive CML. Patients who had been treated with interferon or other targeted anti-cancer therapy which inhibits the growth of leukemic cells Concurrently clinically significant primary malignancy Patients who previously received radiotherapy Patients with impaired cardiac function. uncontrolled chronic medical condition

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
Interventional Model Description: Parallel, 2 arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radotinib 300mg<br>Oral adminstration of Radotinib 300mg BID (600mg/day) for 12months | Drug: Radotinib<br>* Patients randomized to the radotinib arms will receive 300 mg of radotinib BID (1 in the morning and 1 in the evening, at approximately 12-hour intervals).<br>* Other names: Supect;|
| Active Comparator: Imatinib 400mg<br>Oral administration of Imatinib 400mg QD (400mg/day) for 12months | Drug: Imatinib<br>* Patients randomized to the imatinib 400 mg arm will receive imatinib once a day throughout the study.<br>* Other names: Glivec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The MMR rate | The MMR rate at 12 months after radotinib or imatinib treatment in patients with newly diagnosed CML-CP. | at 12 months after radotinib or imatinib treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMR rate | To compare MMR rate for the best response in patients within specific periods. | by 3, 6, 9, and 12 months of treatment. | 
| Complete Cytogenetic Response(CCyR) rate | To compare CCyR rate for the best response in patients within specific periods. | by 3, 6, 9, and 12 months of treatment. | 
| The MR 4.0 and MR 4.5 rates | To compare the MR4.0 and MR4.5 rates for the best response in patients within specific periods. | by 3, 6, 9, and 12 months of treatment, and late | 
| Disease progression (AP/BC) rate | To compare disease progression for the best response in patients within specific periods. | at 3, 6, and 12 months | 
| Failure rate according to European Leukemia Net (ELN) guideline 2013 (ELN 2013*) | To compare failure rate for the best response in patients within specific periods. | at 3, 6, and 12 months |