Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response
Condition: Philadelphia Chromosome Positive; Chronic Myelogenous Leukemia in Chronic Phase
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
Intervention: Nilotinib
Intervention description: 400 mg BID
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic phase; Chronic myelogenous leukemia; CML; Philadelphia chromosome positive; Ph+; Nilotinib; CML-CP; Suboptimal molecular response

Summary:

      To evaluate the major molecular response (MMR) rate at 12 months of nilotinib treatment on
      study in patients with Philadelphia Chromosome Positive (Ph+) chronic myelogenous leukemia in
      chronic phase (CML-CP) who have a suboptimal molecular response to imatinib at 18 months or
      later.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients ≥ 18 years of age.

          2. ECOG 0, 1, or 2.

          3. Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy.

          4. Patients with suboptimal molecular response to imatinib treatment continued for at
             least 18 months (first line therapy)

             Suboptimal molecular response defined as all of the following conditions:

               1. Patients who have achieved CCyR (0% Ph+ chromosomes).

               2. Patients who don't achieve MMR (MMR defined as BCR-ABL/ABL ratio of ≤ 0.1% on the
                  International Scale as detected by RQ-PCR).

             The treatment with imatinib defined as:

             Dose of 300 mg or higher daily must be maintained for a minimum of 3 months prior to
             study entry.

          5. Patients who meet the following laboratory tests criteria:

               1. total bilirubin < 1.5 x ULN,

               2. SGOT and SGPT < 2.5 x ULN,

               3. creatinine < 1.5 x ULN,

               4. Serum amylase and lipase ≤ 1.5 x ULN,

               5. Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.

               6. Serum potassium, phosphorus, magnesium and calcium ≥ LLN or correctable with
                  supplements prior to the first dose of study drug.

          6. Written informed consent prior to any study related screening procedures being
             performed.

        Exclusion Criteria:

          1. Prior accelerated phase or blast crisis CML.

          2. Previously documented T315I mutations.

          3. Presence of chromosomal abnormalities other than Ph+.

          4. Previous treatment with any other tyrosine kinase inhibitor except imatinib.

          5. Impaired cardiac function including any one of the following:

               1. Complete left bundle branch block

               2. Congenital long QT syndrome or family history of long QT syndrome

               3. History of or presence of significant ventricular or atrial tachyarrhythmias

               4. Clinically significant resting brachycardia (<50 bpm)

               5. QTcF > 450 msec on screening ECG

               6. Use of a ventricular-paced pacemaker

               7. Myocardial infarction during the last 12 months

               8. Other clinically significant heart disease (e.g. congestive heart failure,
                  uncontrolled hypertension, unstable angina).

          6. Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine,
             rifampin, rifabutin, rifapentine, phenobarbital, St John's Wort), and the treatment
             cannot be discontinued or switched to a different medication prior to starting study
             drug. See Section 6.4.3 for complete list of these medications.