Evaluating the Safety of Zileuton (Zyflo®) in Combination With Dasatinib (Sprycel®) in Chronic Myelogenous Leukemia

Inclusion Criteria: Target Population: 1\. Patients with CML with known inadequate response (as appropriate for their CML status) to TKIs or known resistance will be considered for this study * Patients who are resistant or not responding adequately to dasatinib as a first line therapy, but are not able or eligible to receive other effective second line treatment can be considered for participation in the study. * Age \> 18 years * ECOG performance status ≤ 2 * Total bilirubin \< 2.0 times the institutional Upper Limit of Normal (ULN) * Hepatic enzymes (AST, ALT ) ≤ 1.5 times the institutional ULN * Serum Na, K+, Mg2+, Phosphate and Ca2+\>= Lower Limit of Normal (LLN) * Serum Creatinine \< 2.3 mg/dL * PT, PTT all Grade 0-1 3) Ability to take oral medication 4) Concomitant Medications * Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy 5) Age and Sex * Women of childbearing potential and men of fathering potential must use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy Exclusion Criteria: 1. Sex and Reproductive Status * Women of childbearing potential and men of fathering potential unable or unwilling to use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy 2. Target Population * Patients intolerant of dasatinib. 3. Medical History and Concurrent Diseases * History of active malignancy during the past 5 years with the exception of nonmetastatic treated skin cancer (e.g. basal or squamous cell carcinoma ) or stage 0 cervical carcinoma * Patients known to be HIV-positive * Patients with active, uncontrolled infections * Concurrent medical condition which may increase the risk of toxicity, including: * Pleural or pericardial effusion of any grade * Cardiac Conditions: * Uncontrolled angina, congestive heart failure or MI within (6 months) * Diagnosed congenital long QT syndrome * Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) * Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec) * Severe cardiac dysfunction (NYHA classification III-IV) * Severe pulmonary disease * History of significant bleeding disorder unrelated to cancer 4. Physical and Laboratory Test Findings * Hepatic dysfunction (serum bilirubin ≥ 2 x ULN, and/or ALT ≥ 3 x ULN, and/or AST ≥ 3 x ULN) * Renal dysfunction (creatinine ≥ 200 μmol/l or 2.3 mg/dl) * Subjects with hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration 5. Allergies and Adverse Drug Reactions * Patients with known allergic reaction or intolerance to either dasatinib or zileuton 6. Prohibited Treatments and/or Therapies * Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: * quinidine, procainamide, disopyramide * amiodarone, sotalol, ibutilide, dofetilide * erythromycin, clarithromycin * chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide * cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. * Patients requiring anticoagulation with Coumadin 7. Other Exclusion Criteria * Prisoners or subjects who are involuntarily incarcerated. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.