Randomized Phase Lll Study of Imatinib Dose Optimization vs Nilotinib in CML Patients With Suboptimal Response to Imatinib

Exclusion Criteria

• •1. Prior accelerated phase including clonal evolution or blast crisis CML;
• •2. Prior therapy with imatinib in combination with any other CML drug other than Hydroxyurea and/or Anagrelide;
• •4.Imatinib therapy started more than 12 months after the date of the original diagnosis; 5.Unable to tolerate imatinib at 400mg; 6.Previous treatment with any other tyrosine kinase inhibitor except Glivec and/or CML therapy other than IFN, hydroxyurea, and /or anagrelide; 7.Myelotoxicity ≥ Grade 2 present at the time of randomization, 8.Previously documented T315I mutations; 9.Impaired cardiac function including one of these:
• •Long QT syndrome or family history of long QT syndrome
• •Clinically significant resting brachycardia (\<50 bpm)
• •QTcF \>450 msec on screening ECG (using the QTcF formula). If QTc \>450 and electrolytes are not with normal ranges, electrolytes should be corrected and then the patient rescreened for QTc to certify QTc \<450 msec;
• •Myocardial infarction ≤ 12 months prior to the first dose of study drug;
• •Other clinically significant heart disease (e.g., CHF, uncontrolled hypertension, unstable angina, significant ventricular or atrial tachyarrhythmias) 10. Impairment of GI function or disease that may significantly alter the absorption of study drug; 11. Treated with strong CYP3A4 inhibitors that cannot be either discontinued or switched to a different medication prior to starting study drug; 12.Currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug; 13.History of previous acute pancreatitis within one year of study entry or medical history of chronic pancreatitis; 14.Known cytopathologically confirmed CNS 15.Women who are pregnant, breast feeding or of a childbearing potential without a negative urine pregnancy test at screening. Female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial and for 3 months post trial end. Post-menopausal women must be ammenorrheic for at least 12 months to be considered of non-childbearing potential; 16. History of another primary malignancy that is currently clinically significant or currently requires active intervention; 17.Any other clinically significant medical or surgical condition which, according to investigators' discretion, should preclude participation; 18.Use of investigational agent within 28 days prior to enrollment; 19.Patients unwilling or unable to comply with the protocol.