Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response

Inclusion criteria

• Male or female patients ≥ 18 years of age.
• ECOG 0, 1, or 2.
• Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy.
• 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:

• Patients who have achieved CCyR (0% Ph+ chromosomes).
• 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.

• Patients who meet the following laboratory tests criteria:

• total bilirubin < 1.5 x ULN,
• SGOT and SGPT < 2.5 x ULN,
• creatinine < 1.5 x ULN,
• Serum amylase and lipase ≤ 1.5 x ULN,
• Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
• Serum potassium, phosphorus, magnesium and calcium ≥ LLN or correctable with supplements prior to the first dose of study drug.
• Written informed consent prior to any study related screening procedures being performed.

Exclusion criteria

• Prior accelerated phase or blast crisis CML.
• Previously documented T315I mutations.
• Presence of chromosomal abnormalities other than Ph+.
• Previous treatment with any other tyrosine kinase inhibitor except imatinib.
• Impaired cardiac function including any one of the following:

• Complete left bundle branch block
• Congenital long QT syndrome or family history of long QT syndrome
• History of or presence of significant ventricular or atrial tachyarrhythmias
• Clinically significant resting brachycardia (<50 bpm)
• QTcF > 450 msec on screening ECG
• Use of a ventricular-paced pacemaker
• Myocardial infarction during the last 12 months
• Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina).
• 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.