Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia

Inclusion Criteria: * Diagnosis of one of the following: * Previously untreated Ph-positive ALL \[either t(9;22) and/or bcr-abl positive\] (includes patients initiated on first course of hyper-CVAD before cytogenetics known) or with lymphoid accelerated or blast phase chronic myelogenous leukemia (CML) * Previously treated Ph-positive ALL or CML (in accelerated phase or blast phase), after 1-2 courses of chemotherapy with or without other tyrosine kinase inhibitors (TKIs) * If they achieved complete response (CR), they are assessable only for event-free and overall survival, or * If they failed to achieve CR, they are assessable for CR, event-free, and overall survival * Performance status ≤ 2 (Eastern Cooperative Oncology Group \[ECOG\] scale, Appendix E) * Adequate liver function as defined by the following criteria: * Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome * Alanine aminotransferase (ALT) ≤ 2 x ULN * Aspartate aminotransferase (AST) ≤ 2.5 x ULN * Adequate pancreatic function as defined by the following criteria: * Serum lipase and amylase ≤ 1.5 x ULN * For females of childbearing potential, a negative pregnancy test must be documented prior to randomization * Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from randomization through 4 months after the end of treatment * Adequate cardiac function as assessed clinically by history and physical examination * Signed informed consent Exclusion Criteria: * Active serious infection not controlled by oral or intravenous antibiotics * History of acute pancreatitis within 1 year of study or history of chronic pancreatitis * History of alcohol abuse * Uncontrolled hypertriglyceridemia (triglycerides \> 450 mg/dL) * Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or squamous cell carcinoma) that in the investigator's opinion will shorten survival to less than 1 year * Active grade III-V cardiac failure as defined by the New York Heart Association criteria * Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: * Any history of myocardial infarction (MI), stroke, or revascularization * Unstable angina or transient ischemic attack prior to enrollment * Congestive heart failure prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment * Diagnosed or suspected congenital long QT syndrome * Any history of clinically significant atrial or ventricular arrhythmias (such as atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or torsades de pointes) as determined by the treating physician * Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (\> 470 msec) unless corrected after electrolyte replacement * Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism * Uncontrolled hypertension (diastolic blood pressure \> 90 mmHg; systolic \> 140 mmHg); patients with hypertension should be under treatment on study entry to effect blood pressure control * Patients currently taking drugs that are generally accepted to have a risk of causing torsades de pointes (unless these can be changed to acceptable alternatives) * Taking any medications or herbal supplements that are known to be strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) within at least 14 days before the first dose of ponatinib * Prior history of treatment with ponatinibfor \> 1 month; patient who has been treated with ponatinib for 1 month prior starting the treatment is eligible * Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator; patient who has been treated with ponatinib for 1 month prior starting the treatment is eligible * Pregnant and lactating women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception; women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months; in addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control * History of significant bleeding disorder unrelated to cancer, including: * Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) * Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) * Patients with documented significant pleural or pericardial effusions unless they are thought to be secondary to their leukemia