|Exclusion Criteria:||1) 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; Complete left bundle branch block; Right bundle branch block plus left anterior or posterior hemi-block; Use of a cardiac 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 rescreened for QTc; History or clinical signs of myocardial infarction within 1 year of study entry; History of unstable angina within 1 year of study entry;|
2) **continued from above: Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension)
3) Severe and/or uncontrolled concurrent 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)
4) History of a positive HIV test (HIV testing is not mandatory)
5) History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
6) Acute or chronic liver, pancreatic, or severe renal disease considered unrelated to study disease
7) History of significant congenital or acquired bleeding disorder
8) Major surgery within 4 weeks prior to Day 1 or those who have not recovered from prior surgery
9) Patients who have received wide field radiotherapy within 4 weeks or limited field radiation for palliation within 2 weeks prior to treatment assignment or who have not recovered from side effects of such therapy
10) 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 entering the study. Medications that are strong CYP3A4 inhibitors should be discontinued for at least 7 days and strong CYP3A4 inducers for at least 2 weeks prior to the study entry.
11) Patients actively receiving therapy with herbal medicines that are CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to entering the study. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo. Herbal medications that are strong CYP3A4 inhibitors should be discontinued for at least 7 days and strong CYP3A4 inducers for at least 2 weeks prior to the study entry
12) Concurrent treatment with CYP2C9 and CYP2B6 substrates with a narrow therapeutic window.
13) 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.
14) 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)
15) Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation (as single BCR-ABL mutation or in combination)
16) Patients who are concurrently receiving any other CML treatment other than nilotinib (including planned stem-cell transplant). Patients may have received hydroxyurea and anagrelide that should have stopped at least 4 weeks before entering the study
17) Patients who have not recovered from side effects related to prior CML therapy </= Grade 2
18) Patients who have received any investigational drug (except nilotinib) </= 4 weeks (or who are within 5 half-lives of a previous investigational drug) prior to starting study treatment or who have not recovered from side effects of such therapy
19) Treatment with any hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, erythropoietin) </= 2 weeks prior to starting study drug or anticipated need of such treatment
20) Prior stem cell transplantation
21) History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer or previous cervical carcinoma in situ
22) (a) Patients who have neuromuscular disorders that are associated with elevated creatine phosphokinase (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy). Patients on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as (but not limited to) HMG CoA inhibitors (statins), clofibrate and gemfibrozil, and cannot be discontinued at least 2 weeks prior to starting LDE225 treatment (b) Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment
23) Breast feeding women and women feeding children with their expressed milk