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

Novartis Pharmaceuticals11 sites in 1 country18 target enrollmentOctober 2008

ConditionsChronic Myelogenous Leukemia - Chronic Phase

InterventionsNilotinib

DrugsNilotinib

Overview

Phase: Phase 2
Intervention: Nilotinib
Conditions: Chronic Myelogenous Leukemia - Chronic Phase
Sponsor: Novartis Pharmaceuticals
Enrollment: 18
Locations: 11
Primary Endpoint: Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

October 2008

End Date

March 2012

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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.

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

Arms & Interventions

Nilotinib

Intervention: Nilotinib

Outcomes

Primary Outcomes

Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels

Time Frame: 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 Outcomes

Number of Participants Who Achieved Major Molecular Response (MMR)(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(From Baseline up to 12 Months)
Median Time to Best Molecular Response(From Start of Study up to End of the Study (up to 41 Months))
Duration of Best Molecular Response(From Start of Study up to End of the Study (up to 41 Months))
Number of Participants With an Event-free Survival(From Start of Study up to End of the Study (up to 41 Months))
Number of Participants With a Progression-free Survival(From Start of Study up to End of the Study (up to 41 Months))
Number of Participants With an Overall Survival(From Start of Study Enrollment up to End of the Study (up to 41 Months))