A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical research study is to compare the confirmed complete cytogenetic response of dasatinib with that of imatinib within 12 months after randomization in patients with newly diagnosed chronic-phase Philadelphia positive chronic myeloid leukemia. The safety of this treatment will also be studied.

Official Title
-----------------
An Open-Label, Randomized, Multicenter Phase III Trial of Dasatinib (SPRYCEL®) vs. Standard Dose Imatinib (400 mg) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia

Conditions
-----------------
Myeloid Leukemia, Chronic

Intervention / Treatment
-----------------
* Drug: Dasatinib
* Drug: Imatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Male or female, aged 18 years and older Chronic phase, Philadelphia Chromosome-positive chronic myeloid leukemia (CML) Eastern Cooperative Oncology Group Performance Status score of 0-2 Key Exclusion Criteria: Pleural Effusion Uncontrolled cardiovascular disease Significant bleeding disorder unrelated to CML Prior treatment with interferon/imatinib/dasatinib/anti-CML systemic treatments except anagrelide/hydroxyurea

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dasatinib<br> | Drug: Dasatinib<br>* Tablets, oral, dasatinib 50-140 mg once daily (QD)<br>* Other names: BMS-354825;|
| Active Comparator: Imatinib<br> | Drug: Imatinib<br>* Tablets, oral, imatinib 200-800 mg, QD<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months | Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR. | Pretreatment, every 3 months up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR) | Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR. Percentage of participants in cCCyR at years 2, 3, 4 and 5 was computed for all randomized participants who achieved cCCyR as measured from the time of first confirmation until the date of progression or death. Participants with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Participants without cCCyR are considered to have progressed on Day 1. | Years 2, 3, 4 and 5 | 
| Percentage of Participants With Major Molecular Response (MMR) at Any Time | Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value). | Planned total follow-up duration of 5 years | 
| Time to Confirmed Complete Cytogenic Response (cCCyR) Overall | The time to cCCyR for all randomized participants is defined as the time from the randomization date until criteria are first met for complete cytogenic response (provided it is confirmed later). The time to cCCyR analysis censors nonresponders who do not progress at their last cytogenetic assessments and nonresponders who progress at the maximum time of all randomized participants. . | Day 1 to 5 years | 
| Time to Major Molecular Response (MMR) Overall | The time to MMR for all randomized participants is defined as the time from randomization date until measurement criteria are first met for MMR. The time to MMR analysis censors nonresponders who do not progress at their last molecular assessments and nonresponders who progress at the maximum time of all randomized participants. | Day 1 to 5 years | 
| Percentage of Participants With Progression-free Survival (PFS) | PFS was defined as the time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date and after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized. | Participants were followed-up for at least 5 years | 
| Percentage of Participants With Overall Survival (OS) | OS was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive. | Participants were followed-up for at least 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia