The main purpose of this protocol is to provide expanded access to the study drug (Ponatinib/AP24534) for people with imatinib-, dasatinib-, and nilotinib- resistant/intolerant Philadelphia Chromosome Positive (Ph+) Leukemias. The other purpose of this protocol is to monitor the safety of the study drug in people with Ph+ Leukemias that have not responded to prior treatment.

Inclusion Criteria:

• Signed and dated informed consent
• Cytogenetic or PCR-based diagnosis of any phase of Ph+ acute lymphoblastic leukemia (ALL) and documented resistance or intolerance to imatinib and a second TKI (nilotinib, dasatinib, bosutinib)
• Eastern Cooperative Oncology Group(ECOG) performance status of 0-2
• Washout from prior anti-proliferative or anti-leukemia treatment: 3 days for hydroxyurea/anagrelide and tyrosine kinase inhibitors
• < Grade 2 or baseline recovery from prior therapy related toxicities (except alopecia)
• At least 3 months post allogeneic stem cell transplantation
• Able to take oral capsules reliably
• AST/ALT less than or equal to 2.5 times ULN, or less than 5 times ULN if attributable to involvement of leukemia
• No active clinical or radiographic pancreatitis
• At least 18 years of age
• Willingness of male and female subjects to use reliable methods of birth control (when applicable)

Exclusion Criteria:

• Subjects with Philadelphia Chromosome and BCR-ABL-negative chronic myeloid leukemia (CML)
• Major surgery or radiotherapy within 7 days before the first dose of Ponatinib (recovery from any previous surgery should be complete before day 1)
• Clinically significant active/uncompensated or uncontrolled cardiac disease (active congestive heart failure; uncontrolled angina or hypertension; myocardial infarction in the past 3 months; clinically significant untreated ventricular arrhythmia; diagnosed or suspected congenital or acquired prolonged QT syndrome; unexplained syncope; history of prolonged QTc)
• Prolonged QTc (> 0.48 sec)
• Pregnant or breastfeeding women
• Evidence of serious active infection, or significant medical or psychiatric illness
• Known seropositivity to HIV, or current acute or chronic Hepatitis B or Hepatitis C (antigen positive), cirrhosis, or clinically significant abnormal lab finding that would, in the investigator's judgment, make the subject inappropriate for this study
• Prior resistance to Ponatinib