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

Phase 2

Terminated

Conditions: Chronic Myelogenous Leukemia - Chronic Phase

Interventions: Drug: Nilotinib

Registration Number: NCT00644878

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 18

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.

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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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nilotinib	Nilotinib	-

Primary Outcome Measures

Name	Time	Method
Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels	From Baseline up to 12 Months	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Achieved Major Molecular Response (MMR)	From Baseline up to 12 Months	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).
Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12	From Baseline up to 12 Months	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.
Median Time to Best Molecular Response	From Start of Study up to End of the Study (up to 41 Months)	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.
Duration of Best Molecular Response	From Start of Study up to End of the Study (up to 41 Months)	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
Number of Participants With an Event-free Survival	From Start of Study up to End of the Study (up to 41 Months)	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.
Number of Participants With a Progression-free Survival	From Start of Study up to End of the Study (up to 41 Months)	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.
Number of Participants With an Overall Survival	From Start of Study Enrollment up to End of the Study (up to 41 Months)	Overall survival was defined as the number of participants from enrollment to the date of death.

Trial Locations

Locations (11): USC Norris Cancer Center Jane Anne Nohl
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Los Angeles, California, United States
St. Agnes Hospital
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Baltimore, Maryland, United States
South Texas Institute of Cancer
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Corpus Christi, Texas, United States
Georgia Health Sciences University Dept. of MCG
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Augusta, Georgia, United States
Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial
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Milwaukee, Wisconsin, United States
University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic
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Iowa City, Iowa, United States
Indiana Blood and Marrow Institute
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Beech Grove, Indiana, United States
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
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New Orleans, Louisiana, United States
Cancer Centers of the Carolinas
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Greenville, South Carolina, United States
Central Utah Clinic Central Utah Clinic (7)
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Provo, Utah, United States
Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr
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Houston, Texas, United States