Study of Molecular Response in Adult Patients on Nilotinib With Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Ph+ CML) in Chronic Phase and a Suboptimal Molecular Response to Imatinib

Study Overview
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Brief Summary
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This exploratory study will evaluate the change in molecular response in chronic myelogenous leukemia - chronic phase patients with a complete cytogenetic response and have a suboptimal molecular response to imatinib

Official Title
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A Multi-center, Open-label, Exploratory Study of Bcr-Abl Kinetics in Adult Patients on Nilotinib With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) and a Suboptimal Molecular Response to Imatinib

Conditions
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Chronic Myelogenous Leukemia - Chronic Phase

Intervention / Treatment
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* Drug: Nilotinib


Participation Criteria
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Eligibility Criteria
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Select Inclusion Criteria: Male or female patients ≥ 18 years of age with a confirmed diagnosis of Ph+ CML-CP and CCyR A suboptimal molecular response to imatinib defined as: Group 1: Treated with 1 year of imatinib, complete cytogenetic response (CCyR) but no major molecular response (MMR) (Bcr-Abl levels >0.1%IS); Group 2: No specific duration of imatinib required, achieved CCyR but has >1 log increase in Bcr-Abl transcript levels Adequate end organ function Patients must have had an imatinib washout period of at least 3 days and not to exceed 7 days prior to the first dose of nilotinib. Group 1 patients must have been treated with imatinib for at least 1 year. There was no imatinib treatment duration requirement for Group 2 patients. For Group 1, patients were eligible for screening if they were treated with an imatinib dose of at least 400mg daily. Dose reduction could have occurred as long as the minimum dose was 300mg daily and the reduction lasted ≤ 28 days. The patient was required to be on 400 mg daily (or a higher dose) of imatinib for at least 6 consecutive months leading up to screening for this study. For Group 2 patients, dose reduction while on imatinib could have occurred as long as the minimum dose was 300 mg daily, and the reduction lasted ≤28 days. Select Exclusion Criteria: Prior accelerated phase or blast crisis CML Patients achieving prior CCyR on imatinib who lost cytogenetic response prior to entering study Previously documented T315I mutations Prior therapy with any other tyrosine kinase inhibitor except imatinib Patients with contraindications to receiving nilotinib, including concomitant medications

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nilotinib<br> | Drug: Nilotinib<br>* Nilotinib 300 mg is taken by mouth twice a day at 12 hour intervals. Nilotinib is to be taken with water on an empty stomach. No food two hours prior to the dose of nilotinib and for one hour following the dose.<br>* Other names: AMN 107;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels | The change on a logarithmic scale at 12 months from a standardized baseline value (100% on the international scale [IS]) in Bcr-Abl transcripts as assessed by peripheral blood Quantitative real-time polymerase chain reaction (RQ-PCR). | From Baseline up to 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Major Molecular Response (MMR) | Major Molecular Response (MMR) value at molecular MD is designated a percentage, which is equivalent to a 3-log reduction from a standardized baseline value from the International Randomized InteYesrferon versus STI571 (IRIS) study or 0.1 percent (%) per International Scale (IS). | From Baseline up to 12 Months | 
| Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12 | Number of participants experiencing either a greater than or equal to (>or=) 1, >or= 2, or >or= 3 log10 reduction in Bcr-Abl transcript levels from Baseline to End of Cycle (EOC) 45 (Day1219 - Day1302) were presented. | From Baseline up to 12 Months | 
| Median Time to Best Molecular Response | The median time to best molecular response, defined as the time (in months) from the date of enrollment to the date when the maximum reduction in Bcr-Abl transcript level was observed. | From Start of Study up to End of the Study (up to 41 Months) | 
| Duration of Best Molecular Response | Duration of best molecular response, defined as the time (in months) from the date of best molecular response to a date when an increase in >1 log10 was observed | From Start of Study up to End of the Study (up to 41 Months) | 
| Number of Participants With an Event-free Survival | Event-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of any of the following: loss of complete hematological response (CHR), loss of Complete cytogenetic response (CCyR), >1 log increase in Bcr-Abl transcripts from the lowest recorded value, progression to accelerated or blast phase, and death. | From Start of Study up to End of the Study (up to 41 Months) | 
| Number of Participants With a Progression-free Survival | Progression-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of progression to Accelerated phase (AP) or Blast crisis (BC) phase, chronic myelogenous leukemia (CML) or death. Participants who did not have an event or dropped out without an event are considered censored at the date of the last observed event. | From Start of Study up to End of the Study (up to 41 Months) | 
| Number of Participants With an Overall Survival | Overall survival was defined as the number of participants from enrollment to the date of death. | From Start of Study Enrollment up to End of the Study (up to 41 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leukemia, chronic myelogenous leukemia, chronic phase, molecular response, nilotinib, ENABL