Inclusion Criteria:

1. Male and female patients 18 years or older. 2. Diagnosis of CML-CP according to the World Health Organization. 3. Patients with CML-CP under first-line treatment with nilotinib at the approved daily dose of 300 mg BID mg for at least 3 calendar years. Note: At study entry, an ongoing treatment at a dose ≥400 mg per day is allowed. 4. Sustained DMR defined as ≥ MR 4.0 (BCR-ABL level ≤0.01% IS) in all of the last 4 BCR-ABL RQ-PCR assessments with a minimum interval between each assessment of 3 months and a maximum interval of 6 months. 5. Patient must meet the following laboratory values at the screening visit:

• - Absolute Neutrophil Count ≥1.0 x 109/L.

• - Platelets ≥75 x 109/L.

• - Hemoglobin (Hgb) ≥ 9 g/dL.

• - Serum creatinine < 1.5 mg/dL.

• - Aspartate transaminase (AST) ≤ 3.0 x Upper Limit of Normal (ULN) - Alanine transaminase (ALT) ≤ 3.0 x ULN.

• - Serum lipase ≤ 2 x ULN.

6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 7. Study subjects must be able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

1. Patients with known atypical transcript. 2. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past). 3. Dose reductions/interruptions due to neutropenia or thrombocytopenia in the past 6 months. 4. Patient ever attempted to permanently discontinue nilotinib treatment. 5. Known impaired cardiac function including any one of the following:

• - Inability to determine QT interval on ECG.

• - Complete left bundle branch block.

• - 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.

• - QTcF > 480 msec.

• - History or clinical signs of myocardial infarction within 1 year prior to study entry.

• - History of unstable angina within 1 year prior to study entry.

• - Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension) 6.

Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol. 7. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis. 8. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer. 9. History of other active malignancy within 5 years prior to study entry except for previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ treated curatively. 10. Patients who have not recovered from prior surgery. 11. Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1. 12. 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). 13. 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 study entry. 14. 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 study entry. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo. 15. Pregnant or nursing (lactating) women. 16. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 14 days after stopping medication. There is a limited amount of data on pregnancies in patients while attempting treatment-free remission (TFR). If pregnancy is planned during the TFR phase, the patient must be informed of a potential need to re-initiate treatment with nilotinib during pregnancy. Highly effective contraception methods include:

• - Total abstinence (when this is in line with the preferred and usual lifestyle of the subject.

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), total 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 screening).

The vasectomized male partner should be the sole partner for that subject.

• - Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.

In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before starting the study. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. 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 childbearing potential.

The purpose of the present study is to evaluate the rate of full treatment-free molecular remission in a selected population of CML-CP patients treated with nilotinib at half the standard dose during a consolidation period of 12 months, followed by complete therapy cessation. The study is made up of 4 phases:

• - Screening (week -4 - week 0) - Nilotinib consolidation (week 0 - week 48) - Nilotinib treatment-free remission (TFR) phase (week 48 - week 144) - Follow up phase Patients fulfilling this protocol-specific definition of sustained deep molecular response (DMR) and all other inclusion/exclusion criteria will start the consolidation phase of the study.

During Nilotinib consolidation (week 0

• - week 48) period, patients will be treated with nilotinib 300 mg QD.

At the end or during the consolidation period, patients will proceed as follows:

• - Patients with sustained DMR at the end of the consolidation phase will enter the tretament-free remission (TFR) phase and nilotinib will be discontinued.

• - Patients with loss of major molecular response (MMR) at any time during the consolidation phase will enter the follow-up phase and will return to the standard nilotinib administration regimen (nilotinib 300 mg BID) until the end of the trial (week 144).

Loss of MMR is defined as breakpoint cluster region--c-abl oncogene 1 (BCR-ABL) >0.1% international scale assessed in a single blood sample and will mandate reinitiation of nilotinib treatment at 300 mg BID within 5 weeks after the collection of the blood sample demonstrating loss of MMR.

• - Patients with more than MMR, but without meeting the definition of sustained DMR, will remain in the consolidation phase and will be treated with nilotinib 300 mg QD until the end of the trial (week 144).

During the TFR phase, BCR-ABL levels will be monitored every month for the first year at weeks 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96 and then every three months until the end of the study at weeks 108, 120, 132 and 144 (end of study) or whenever clinically indicated at the discretion of the investigator. The primary objective will be evaluated at week 96. During the TFR phase, loss of MMR will cause reinitiation of nilotinib treatment at 300 mg BID. Follow up phase for patients who were discontinued from the trial, starting from the date of trial discontinuation up to the end of the trial (144 week), and for patients with loss of MMR at any time during the study. Patients discontinued from the treatment for any reason will be followed for survival information every 3 months until week 144. All patients still on study treatment at the end of the study will be transitioned to prescription nilotinib.

Arms

Experimental: Nilotinib

Oral 300 mg hard capsules taken once a day

Interventions

Drug: - Nilotinib

Nilotinib oral 300 mg QD hard capsules