A Phase III Multi-center, Open-label, Randomized Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Inclusion Criteria

Inclusion criteria:

- ECOG 0, 1, or 2.

- Patients with CML-CP within 6 months of diagnosis (date of initial diagnosis is the
date of first cytogenetic analysis). Standard conventional cytogenetic analysis must
be done on bone marrow. (FISH cannot be used)

- Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic
confirmation of Philadelphia chromosome of (9;22) translocations (presence of
BCR-ABL: a review of a minimum 20 metaphases is required.).

- Documented chronic phase CML will meet all the criteria defined by:

- < 15% blasts in peripheral blood and bone marrow

- < 30% blasts plus promyelocytes in peripheral blood and bone marrow

- < 20% basophils in the peripheral blood

- ≥ 100 x 109/L (≥ 100,000/mm3) platelets

- No evidence of extramedullary leukemic involvement, with the exception of
hepatosplenomegaly

- Adequate end organ function as defined by:

- 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.

- Female patients of childbearing potential must have a negative serum pregnancy test
within 7 days before initiation of study drug.

- Patients must have the following laboratory values (≥ LLN (lower limit of normal) or
corrected to within normal limits with supplements prior to the first dose of study
medication.):

- Potassium ≥ LLN

- Magnesium ≥ LLN

- Phosphorus ≥ LLN

- Total calcium (corrected for serum albumin) ≥ LLN.

- Ability to provide written informed consent prior to any study related screening
procedures being performed.

Exclusion criteria:

- Patients who are considered to be Philadelphia chromosome negative because they do
not have a confirmed cytogenetic diagnosis of Philadelphia chromosome (9,22
translocation) positive CML.

- Previously documented T315I mutations.

- Treatment with tyrosine kinase inhibitor(s) prior to study entry is not allowed,
except in the following situation: in emergent cases where the patient requires
disease management while awaiting study start, commercial supplies of Gleevec/Glivec
at any dose may be prescribed to the patient but for no longer than 2 weeks in
duration.

- Any medical treatment for CML prior to study entry for longer than 2 weeks with the
exception of hydroxyurea and/or anagrelide

- Impaired cardiac function including any one of the following:

- LVEF < 45% or below the institutional lower limit of the normal range (whichever is
higher) as determined by locally read echocardiogram

- Inability to determine the QT interval on ECG

- Complete left bundle branch block

- Use of a ventricular-paced pacemaker

- Congenital long QT syndrome or a known family history of long QT syndrome.

- History of or presence of clinically significant ventricular or atrial
tachyarrhythmias

- Clinically significant resting bradycardia (<50 beats per minute)

- QTc > 450 msec on the average of three serial baseline ECG (using the QTcF formula)
as determined by central reading. If QTcF >450 msec and electrolytes are not within
normal ranges, electrolytes should be corrected and then the patient re-screened for
QTc

- History of clinically documented myocardial infarction

- History of unstable angina (during the last 12 months)

- Other clinically significant heart disease (e.g., congestive heart failure or
uncontrolled hypertension).

- Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS
involvement, lumbar puncture not required).

- Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, 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.

- Treatment with other investigational agents (defined as not used in accordance with
the approved indication) within 30 days of Day 1.

- History of non-compliance to medical regimens or inability to grant consent.

- Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol,
phenprocoumon)

- Patients with another primary malignancy except if the other primary malignancy is
neither currently clinically significant or requiring active intervention

- Patients actively receiving therapy with strong CYP3A4 inhibitors (e.g.,
erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin,
telithromycin, ritonavir, mibefradil) and the treatment cannot be either discontinued
or switched to a different medication prior to starting study drug. See link for
complete list of these medications: http://medicine.iupui.edu/flockhart/table.htm.
Novartis must be contacted if a patient needs to be started on any of these drugs
during study treatment.

- Patients actively receiving therapy with strong CYP3A4 inducers (e.g., dexamethasone,
phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbitol, St. John's
Wort) and the treatment cannot be either discontinued or switched to a different
medication prior to starting study drug. See link for complete list of these
medications: http://medicine.iupui.edu/flockhart/table.htm. Novartis must be
contacted if a patient needs to be started on any of these drugs during study
treatment.

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass
surgery)

- History of acute pancreatitis within 1 year of study entry or past medical history of
chronic pancreatitis.

- Acute or chronic liver, pancreatic or severe renal disease considered unrelated to
disease.

- Patients who are 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 (Please see
http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a
comprehensive list of agents that prolong the QT interval)

- Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential
without a negative pregnancy test prior to baseline and (d) female of childbearing
potential unwilling to use contraceptive precautions throughout the trial
(post-menopausal women must be amenorrheic for at least 12 months to be considered of
non-childbearing potential)

Other protocol-defined inclusion/exclusion criteria may apply