Safety and Efficacy Study of Nilotinib Combined With Mitoxantrone, Etoposide, and High-dose Cytarabine Induction Chemotherapy Followed by Consolidation for Patients With C-kit Positive Acute Myeloid Leukemia

Inclusion Criteria: * AML as defined by WHO (World Health Organization) criteria, all subtypes except APL (acute promyelocytic leukemia). * One of the following poor risk features: 1. Persistent leukemia (at least 10% bone marrow blasts) after induction therapy, consisting of cytarabine 100-200 mg/m2 plus an anthracycline. 2. Relapse within two years of achieving complete remission with such induction therapy. Any consolidation therapy is acceptable, including stem cell transplantation. 3. No prior inductions, but antecedent myeloproliferative disorder or CMML (chronic myelomonocytic leukemia) (These patients are given NOVE-HiDAC as frontline therapy at Princess Margaret Hospital). * Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry. For relapsed patients, this will be assessed at the time of relapse. For primary induction failures the initial diagnostic sample may be used. * Age 18-65. * ECOG performance status \< 3 (see Appendix I). * Patients must have the following laboratory values within normal limits (WNL) at the local institution lab or corrected to WNL with supplements prior to first dose of study medication. 1. Potassium (WNL) 2. Magnesium (WNL) * No chemotherapy within the previous four weeks, other than hydroxyurea to control counts. Hydroxyurea may be continued up to Day 4 of treatment with nilotinib. If hydroxyurea is used, it must be stopped at least 48 hours prior to starting chemotherapy. * Able to give informed consent. Exclusion Criteria: * Active uncontrolled infection. * Active CNS (central nervous system) leukemia * Serum creatinine \> 200 umol/L. * Serum bilirubin \> 1.5 x ULN, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) \> 2x ULN (upper limit of normal). * Serum amylase and lipase \> 1.5x ULN * Left ventricular ejection fraction \< 50% * Impaired cardiac function including any of the following: 1. Long QT syndrome or a known family history of long QT syndrome 2. History or presence of clinically significant ventricular or atrial tachyarrhythmias 3. Clinically significant resting bradycardia (\< 50 beats per minute) 4. Inability to monitor the QT interval by ECG 5. QTc \> 450 msec on baseline ECG (electrocardiogram). If QTc \> 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc 6. Myocardial infarction within 1 year of starting study drug 7. Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension) * Patients currently receiving treatment with strong CYP3A4 inhibitors as listed in Section 5.8 and treatment cannot be either discontinued or switched to a different medication prior to starting study drug. * Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug * History of acute or chronic pancreatic disease. * Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Male or female patients of childbearing potential unwilling to use contraceptive precautions throughout the trial and 3 months following discontinuation of study drug. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of nilotinib. * Known hypersensitivity to study drugs or other components.