Cardiovascular Assessment of Ponatinib as Third Line Treatment in Chronic Phase Chronic Myeloid Leukemia

Inclusion Criteria: 1. Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures. 2. CML diagnosis, Chronic Phase (CP), treated with imatinib and bosutinib. Previous treatment with dasatinib or nilotinib will not be allowed. 3. Resistant or intolerant to imatinib and/or bosutinib. 4. Able to take oral therapy. 5. Female or male, 18 years of age or older. 6. ECOG performance status 0-2. 7. Minimum life expectancy of 3 months or more. 8. Adequate organ function as defined by the following criteria: * Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy * Total serum bilirubin ≤ 1.5 x ULN (except patients with documented Gilbert's syndrome) * Creatinine ≤ 1.5 x ULN * Prothrombin time (PT) \< 1.5 × ULN * Lipase ≤ 1.5 × ULN for institution * Amylase ≤ 1.5 × ULN for institution 9. Normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females. 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 11. Female and male patients who are of childbearing potential must agree to use an effective form of contraception (2 forms of contraception) with their partners throughout participation in this study and for at least 90 days after the last dose of treatment. 12. For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment. Exclusion Criteria: 1. Current treatment on another therapeutic clinical trial. 2. Received TKI therapy within 7 days prior to receiving the first dose of ponatinib, or 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 on-going 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. 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. 8. 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. 9. Have a significant bleeding disorder unrelated to CML or Ph+ ALL. 10. Have a history of pancreatitis or alcohol abuse. 11. Have uncontrolled hypertriglyceridemia (triglycerides \> 450 mg/dL). 12. Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib. 13. 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). 14. Pregnancy or breastfeeding. 15. 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. 16. 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. 17. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration.