Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations (MACS1148)

• To determine the proportion of ELN-defined optimal responses on nilotinib. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
• To determine the rate and time to loss of CCyR, MMR and CMR on nilotinib. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
• To determine the time to and duration of the CCyR, MMR and CMR achieved on nilotinib. [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
• To determine EFS, PFS and OS with up to 2 years of nilotinib treatment and overall safety profile [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

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.

• CML
• Philadelphia Chromosome Positive (Ph+)
• Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels

• Drug: nilotinib
  All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours
  Other Names:

  • AMN107
  • Tasigna
• Drug: AMN107

Inclusion Criteria:

• Ph+ CML-CP within 12 months of diagnosis
• Imatinib 400 mg qd for up to 12 months
• Imatinib trough plasma concentration <850 ng/mL

• Patient that have met response milestones including:

  1. CHR and at least minor CyR (Ph+ ≤65%) at 3 months from diagnosis
  2. At least pCyR at 6 months from diagnosis (Ph+ ≤35%)
  3. CCyR at 12 months from diagnosis

Exclusion Criteria:

• Prior documented failure events including:
• Loss of CHR or CCyR
• Less than CHR (stable disease or disease progression) at 3 months after diagnosis
• No CyR at 6 months after diagnosis
• Less than PCyR at 12 months after diagnosis
• Prior accelerated phase or blast phase CML
• Previously documented T315I mutation
• Previous treatment with any other tyrosine kinase inhibitor except for imatinib.
• Patients who had any other treatment for CML (transplant) except imatinib, hydroxyurea and/or anagrelide
• Impaired cardiac function (refer to Section 5.2 for details)
• 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.