Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations

A Multi-center, Single Arm Study of Nilotinib in Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Patients With Low Imatinib Trough Plasma Concentrations

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.

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