Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
Condition: CML; Philadelphia Chromosome Positive (Ph+); Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
Intervention: nilotinib
Intervention description: All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Philadelphia chromosome positive; Ph+; chronic myelogenous leukemia chronic phase; CML-CP; low imatinib trough levels

Summary:

      This study is to determine the number of European Leukemia Network (ELN)guideline defined
      treatment failure events from time of study entry in CML-CP patients with low imatinib trough
      concentrations treated with nilotinib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cytogenetically confirmed Ph+ CML-CP Any prior dose of Imatinib

          -  Imatinib 400 mg daily for ≥7 consecutive days prior to imatinib trough collection

          -  Imatinib trough plasma concentration <850 ng/mL

        Exclusion Criteria:

          -  Prior documented failure events as defined by ELN guidelines:

          -  Loss of CHR, CCyR, or clonal progression/Ph+

          -  Less than CHR at 3 months after diagnosis

          -  No CyR at 6 months after diagnosis

          -  Less than PCyR at 12 months after diagnosis

          -  Less than CCyR at 18 months after diagnosis

          -  Prior accelerated phase or blast phase CML

          -  Previously documented T315I mutation

          -  Previous treatment for CML with any other tyrosine kinase inhibitor except for
             imatinib

          -  Patients who had any other treatment for CML (transplant) except interferon +/- ara-
             C, imatinib, hydroxyurea and/or anagrelide

          -  Impaired cardiac function

          -  Patients receiving therapy with strong inhibitors of CYP3A4 or medications that
             prolong the QT interval and cannot be either discontinued or switched to a different
             medication prior to starting study drug.

          -  Any other malignancy that is clinically significant or requires active intervention.

          -  Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from
             prior surgery

          -  Treatment with other investigational agents within 30 days of Day 1

          -  Women who are pregnant, breast feeding, or of childbearing potential without a
             negative serum test at baseline. Post-menopausal women must be amenorrhoeic for at
             least 12 months to be considered of non-childbearing potential. Women of childbearing
             potential must have a negative serum pregnancy test within 7 days of the first dose of
             nilotinib

          -  Sexually active male and female patients taking nilotinib unwilling to use adequate
             contraception throughout the trial and 3 months following discontinuation of study
             drug