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
Condition: Chronic Myelogenous Leukemia - Chronic Phase
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Philadelphia Chromosome
Intervention: Nilotinib
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: leukemia; chronic myelogenous leukemia; chronic phase; molecular response; nilotinib; ENABL

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
    

Eligibility criteria:

        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