Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Study Overview
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Brief Summary
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In this study, the efficacy and safety of nilotinib 400 mg twice daily, will be compared with imatinib 400 mg twice daily in patients with a suboptimal response to imatinib for their Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

Detailed Description
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This trial was to evaluate the CCyR rate at 12 months of nilotinib therapy when compared to imatinib treatment in patients with suboptimal response to imatinib. The patients were stratified by prior duration of initial imatinib treatment, and were randomized to receive either 400 mg/twice daily of continuous nilotinib or imatinib treatment. The first stratum patients were treated with imatinib = 6 to < 12 months and having at least a minimal cytogenetic, but no partial cytogenetic response; and the second stratum patients were treated with imatinib = 12 months to < 18 months and having partial cytogenetic response (PCyR), but no CCyR.

Official Title
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A Phase III Randomized, Open- Label Multi-center Study of Nilotinib Versus Imatinib in Adult Patients With Ph+ Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Cytogenetic Response (CyR) on Imatinib

Conditions
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Myelogenous Leukemia

Intervention / Treatment
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* Drug: Imatinib
* Drug: Nilotinib (AMN107)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of Philadelphia chromosome positive chronic myelogenous leukemia in the chronic phase. Patients with suboptimal cytogenetic response to a dose of 400 mg imatinib (first line therapy) defined as: 6 to < 12 months of treatment and -have 36 - 95% Ph+ metaphases, or 12 to <18 months of treatment and have 1 - 35% Ph+ metaphases (Standard cytogenetics, no FISH [fluorescence in situ hybridization] analysis was allowed). Exclusion criteria: Patient who have received more than 18 months of imatinib therapy Patients who have achieved partial or complete cytogenetic response and lost that response prior to entering the study. Prior treatment with greater than 400 mg/day imatinib. Uncontrolled or significant cardiovascular disease. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon) Currently taking certain medications that could affect the rhythm of your heart. Other protocol-defined inclusion/exclusion criteria may apply

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 |
| --- | --- |
| Experimental: Nilotinib (AMN107)<br> | Drug: Nilotinib (AMN107)<br>* Administered orally as a single agent on a continuous daily schedule of 400 mg bid (2 x 200 mg twice daily) without food. Once cycle comprised of 28 days.<br>|
| Active Comparator: Imatinib<br> | Drug: Imatinib<br>* Administered orally as a single agent on a continuous daily schedule given 400 mg bid (twice daily) with food. One cycle comprised of 28 days.<br>* Other names: Gleevec®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib | Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Durable Complete Cytogenetic Response Rate | Due to early termination of the trial, the number of patients was too small and imbalanced and therefore analysis was not performed. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic leukemia, leukemia, bone marrow, leukemia symptoms, cml, complete blood count, lymphocyte, blood cancer, leukocytes, bone marrow biopsy, leukemia research, leukemia cells, bone marrow disease, chronic myeloid leukemia, blood cancer symptoms, white blood cell diseases, chronic myelogenous leukemia, leukemia treatment, leukemia facts, leucemia, facts about leukemia, myelogenous leukemia, newly diagnosed CML, suboptimal response, Philadelphia chromosome positive (Ph+), chronic myelogenous leukemia in chronic phase (CML-CP)