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

Inclusion Criteria

• Male or female patients ≥ 18 years of age
• 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 daily 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 9%)
• Impaired cardiac function including any one of the following:
• LVEF 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
• 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 (e.g. uncontrolled diabetes, uncontrolled infection)
• 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 who have not recovered from prior surgery
• 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.
• 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. (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