Inclusion Criteria:

1. Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL, as
follows:

- All patients must have screening bone marrow (BM) cytogenetics with conventional
banding performed within 42 days prior to beginning treatment.

- Examination of at least 20 metaphases is required in patients in CP. If less
than 20 metaphases are examined, the BM aspirate must be repeated.

- Adequate BM aspirate with differential cell counts is required in patients with
AP, BP, or Ph+ ALL. If an adequate aspirate is not obtained, the aspirate must
be repeated.

2. Be previously treated with and resistant, or intolerant, as defined in the protocol,
to either dasatinib or nilotinib for CML or at least one TKI for Ph+ ALL, regardless
of whether dasatinib or nilotinib or the prior TKI were used to treat newly diagnosed
or resistant patients.

3. Must be ≥ 18 years old.

4. Provide written informed consent.

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

6. Minimum life expectancy of 3 months or more.

7. Adequate renal function defined as serum creatinine < 1.5 × upper limit of normal
(ULN) for institution.

8. Adequate hepatic function defined as:

1. Total bilirubin < 1.5 × ULN

2. Alanine aminotransferase (ALT [SGPT]) and aspartate aminotransferase (AST
[SGOT]) < 2.5 × ULN for institution (< 5 × ULN if liver involvement with
leukemia)

3. Prothrombin time < 1.5 × ULN

9. Normal pancreatic status defined as:

1. Lipase ≤ 1.5 × ULN for institution

2. Amylase ≤ 1.5 × ULN for institution

10. Normal QT interval corrected (Fridericia) (QTcF) interval on screening ECG
evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females.

11. For females of childbearing potential, a negative pregnancy test must be documented
prior to enrolment.

12. Female and male patients who are of childbearing potential must agree to use an
effective form of contraception with their sexual partners throughout participation
in this study.

13. Ability to comply with study procedures, in the Investigator's opinion.

Exclusion Criteria:

Patients are not eligible for participation in the study if they meet any of the following
exclusion criteria:

1. Received TKI therapy within 7 days prior to receiving the first dose of ponatinib, or
have not recovered (> grade 1 by National Cancer Institute Common Terminology
Criteria for Adverse Events, version 4.0 [NCI CTCAE v.4.0]) from adverse events (AEs)
(except alopecia) due to agents previously administered.

2. Received other therapies as follows:

1. For CP and AP patients, received interferon, cytarabine, or immunotherapy within
14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational
therapy within 28 days prior to receiving the first dose of ponatinib.

2. For BP patients, received chemotherapy within 7 days prior to the first dose of
ponatinib. Otherwise, 2a applies.

3. For Ph+ ALL patients, received corticosteroids within 24 hours before the first
dose of ponatinib and other chemotherapy within 7 days prior to the first dose
of ponatinib. Otherwise, 2a applies.

4. All patients are excluded if they have not recovered (> grade 1 by NCI CTCAE
v.4.0) from AEs (except alopecia) due to agents previously administered.

3. Underwent autologous or allogeneic stem cell transplant < 60 days prior to receiving
the first dose of ponatinib; any evidence of ongoing graft versus-host disease (GVHD)
or GVHD requiring immunosuppressive therapy.

4. Take medications that are known to be associated with Torsades de Pointes.

5. Require concurrent treatment with immunosuppressive agents, other than
corticosteroids prescribed for a short course of therapy.

6. Have previously been treated with ponatinib.

7. Patients with CP-CML are excluded if they are in CCyR.

8. Patients with CP-CML are excluded if a baseline BM aspirate adequate for conventional
cytogenetic analysis with 20 metaphases examined is not available.

9. Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if they are in MaHR.

10. Patients with AP-CML, BP-CML, or Ph+ ALL are excluded if a baseline BM aspirate
adequate for cell count and differential report is not available. Patients with a
fibrotic marrow or dry tap that does not yield adequate cell counts for diagnosis are
not evaluable for classification, and endpoints are not eligible.

11. Have active central nervous system (CNS) disease as evidenced by cytology or
pathology. In the absence of clinical CNS disease, lumbar puncture is not required.
History itself of CNS involvement is not exclusionary if CNS has been cleared with a
documented negative lumbar puncture.

12. Have significant or active cardiovascular disease, specifically including, but not
restricted to:

1. Myocardial infarction within 3 months prior to first dose of ponatinib

2. History of clinically significant atrial arrhythmia or any ventricular
arrhythmia

3. Unstable angina within 3 months prior to first dose of ponatinib

4. Congestive heart failure within 3 months prior to first dose of ponatinib

13. Have a significant bleeding disorder unrelated to CML or Ph+ ALL.

14. Have a history of pancreatitis or alcohol abuse.

15. Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL).

16. Have malabsorption syndrome or other gastrointestinal illness that could affect
absorption of orally administered ponatinib.

17. Have been diagnosed with another primary malignancy within the past 3 years (except
for non-melanoma skin cancer or cervical cancer in situ, or controlled prostate
cancer, which are allowed within 3 years).

18. Are pregnant or lactating. Women of childbearing potential must agree to an
effective contraception from the time of signing the informed consent through the
Follow-up Visit, approximately 30 days after last dose of ponatinib.

19. Underwent major surgery (with the exception of minor surgical procedures, such as
catheter placement or BM biopsy) within 14 days prior to first dose of ponatinib.

20. Have ongoing or active infection (including known history of human immunodeficiency
virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]). Testing for these
viruses is not required in the absence of history.

21. Suffer from any condition or illness that, in the opinion of the Investigator or the
Medical Monitor, would compromise patients safety or interfere with the evaluation of
the safety of the study drug.