Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients

Inclusion Criteria:

- Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of
nilotinib treatment prior to pre-screening at approved total dialy dose of 600 mg BID
or at a reduced dose of 400 mg QD if required from the perspective of tolerance for
BCR-ABL positive CML in documented chronic phase at the time of diagnosis

- Evidence of typical BCR-ABL transcripts (b3a2 and/or b2a2) at the time of CML-CP
diagnosis i.e. prior to first start of TKI treatment which are amenable to
standardized RT-PCR quantification"

- Patient in MR4.5 at prescreening at Novartis designated lab

- ECOG performance status of 0-2

- Adequate end organ function as defined by:

- Direct bilirubin ≤ 1.5 x ULN except for i) patients with documented Gilbert's
syndrome for whom any bilirubin value is allowed and ii) for patients with
asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase
within normal range).

- SGOT(AST) and SGPT(ALT) ≤ 3 x ULN i.e. equivalent to ≤ Grade 1 NCI-CTCAE v.4.03

- Serum lipase ≤ 2 x ULN i.e. equivalent to ≤ Grade 2 NCI-CTCAE v.4.03

- Alkaline phosphatase ≤ 2.5 x ULN

- Serum creatinine < 1.5 x ULN

- Patients must have the following electrolyte values within normal limits or corrected
to be within normal limits with supplements prior to first dose of study medication:

- Potassium (suggested keep to prevent issues with QT and/or rhythm abnormalities)

- Magnesium (suggested keep to prevent issues with QT and/or rhythm abnormalities)

- Total calcium (corrected for serum albumin)

- Patients must have normal marrow function as defined:

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 10E9/L

- Hemoglobin ≥ 9.0 g/dL

- Platelets ≥ 100 x 10E9/L

Exclusion Criteria:

- Previous treatment with BCR-ABL inhibitors other than nilotinib for more than a total
cumulative duration of 4 weeks

- Previous treatment with alpha-interferon of any duration

- Previous anticancer agents for CML other than nilotinib except for cytoreduction after
CML diagnosis until up to 4 weeks after first dose of nilotinib

- Known second chronic phase of CML after previous progression to AP/BC

- Poorly controlled diabetes mellitus (defined as HbA1c > 9%)

- Impaired cardiac function including any one of the following:

- LVEF < 45% or below the institutional lower limit of the normal range (whichever
is higher)

- Inability to determine the QT interval on ECG, except for patients with evidence
of measurable QT interval at the time of CML diagnosis (e.g. prior to first start
of TKI treatment) and who have no documented clinical signs of cardiovascular
disease and/or clinical signs of conduction abnormality.

- Complete left bundle branch block

- Right bundle branch block plus left anterior or posterior hemiblock

- 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

- QTc > 450 msec on the average of three serial baseline ECG (using the QTcF
formula). If QTcF > 450 msec and electrolytes are not within normal ranges,
electrolytes should be corrected and then the patient re-tested for QTc.This
exclusion criterion is not applicable for patients with non-measurable QT
interval who have evidence of measurable QT interval at the time of CML diagnosis
(e.g. prior to first start of TKI treatment) and who have no documented clinical
signs of cardiovascular disease and/or clinical signs of conduction abnormality.

- History or clinical signs of myocardial infarction within 1 year of study entry

- History of unstable angina within 1 year of study entry

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

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

- Known presence of significant congenital or acquired bleeding disorder unrelated to
cancer

- History of another active malignancy within 5 years prior to study entry with the
exception of previous or concomitant basal cell skin cancer and previous carcinoma in
situ treated curatively

- Treatment with other investigational agents (defined as not used in accordance with
the approved indication) within 4 weeks of Day 1

- Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and
the treatment cannot be either discontinued or switched to a different medication
prior to starting study drug. See Appendix 1 for a list of these medications. This
list may not be exhaustive.

- Patients actively receiving therapy with herbal medicines that are strong CYP3A4
inhibitors and/or inducers, and the treatment cannot be either discontinued or
switched to a different medication prior to starting study drug. These herbal
medicines may include Echinacea, (including E. purpurea, E. angustifolia and E.
pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo.

- Patients who are currently receiving treatment with any medications that have the
potential to prolong the QT interval and the treatment cannot be either safely
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 list of agents that prolong the QT interval)

- 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)

- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test.

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during the study and for 14 days after the final dose of nilotinib. Highly effective
contraception is defined as either:

- Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception

- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment.
In case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment.

- Male sterilization (at least 6 months prior to enrolling). For female patients on
the study the vasectomized male partner should be the sole partner for that
patient.

- Use of a combination of any two of the following:

1. Use of oral, injected or implanted hormonal methods of contraception or
other forms of hormonal contraception that have comparable efficacy (failure
rate <1%), for example hormone vaginal ring or transdermal hormone
contraception.

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS)

3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository In case of use of oral contraception women should have been
stable on the same pill for a minimum of 3 months before taking study
treatment Women are considered post-menopausal and not of child bearing
potential if they have had 12 months of natural (spontaneous) amenorrhea
with an appropriate clinical profile (e.g. age appropriate, history of
vasomotor symptoms) or have had surgical bilateral oophorectomy (with or
without hysterectomy) or tubal ligation at least six weeks prior to
enrolling. In the case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment
is she considered not of child bearing potential.

If a study patient becomes pregnant or suspects being pregnant during the study or within
30 days after the final dose of nilotinib, the Study Doctor needs to be informed
immediately and ongoing study treatment with nilotinib has to be stopped immediately.

Other protocol-defined inclusion/exclusion criteria may apply.