Efficacy of Nilotinib Versus Imatinib in Ph+ CML in Early CP Who Have a Suboptimal Molecular Response to Imatinib

Inclusion Criteria:

* Male or female patients ≥ 18 years of age
* ECOG 0, 1, or 2
* Diagnosis of Ph+ CML in CP
* Patients with suboptimal molecular response defined as:

  * Patients must achieve a CCyR at 12 months and must maintain CCyR until study entry (0% Ph+ chromosomes). Cytogenetic confirmation of Ph+ (9;22 translocation) is required on a minimum of 20 metaphases. FISH analysis will not be accepted.
  * at least 18 months and up to 24 months (≥18 to ≤24 months) of treatment with imatinib as first line therapy, at a dose of 400 mg daily, without achieving a MMR (\<0.1% IS of Bcr-Abl transcript by RQ- PCR).
* The following laboratory results must be present:

  * 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, magnesium and calcium ≥ LLN or correctable with supplements to within normal limits prior to the first dose of study medication.
* Ability to provide written informed consent prior to any study related screening procedures being performed.

Exclusion Criteria:

* Late CP who started imatinib more than 6 months after diagnosis
* Prior accelerated phase or blast phase CML
* Rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose galactose malabsorption
* Hypersensitivity to nilotinib or any of the excipients.
* Previously documented T315I mutations.
* Intolerance to imatinib 400 mg daily defined as the inability to maintain at least 400 mg daily for the previous 3 months.
* Patients treated with imatinib more than 400mg daily
* Achieved prior MMR or CCyR on imatinib and lost response to entering the study.
* Previous treatment with interferon or any other tyrosine kinase inhibitor except imatinib (however, allow hydroxyurea or anagrelide before initial imatinib start)
* Impaired cardiac function
* Treatment with inhibitors of CYP3A4 or medications well documented to prolong the QT interval are contraindicated
* Impaired gastrointestinal (GI) function or GI disease
* History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
* Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
* Any other malignancy that is clinically significant or requires active intervention.
* Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, acute or chronic liver disease, pancreatic, or severe renal disease unrelated to tumor, active or uncontrolled infection).
* History of significant congenital or acquired bleeding disorder unrelated to cancer.
* Previous radiotherapy to ≥ 25% of the bone marrow.
* Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery.
* Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon).
* Treatment with other investigational agents within 30 days of Day 1.
* History of non-compliance to medical regimens or inability to grant consent.
* Women who are pregnant, breast feeding, or of childbearing potential without a negative serum or urine pregnancy test at baseline.