Safety and Efficacy of Ponatinib Followed by Imatinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase

Inclusion Criteria: * Male or female patients aged ≥18 and ≤65 years at time of inform consent signature. * Cytologically confirmed CML, Philadelphia chromosome positive with or without additional chromosomal abnormalities and/or BCR-ABL positive (Major BCR (M-BCR) transcript exclusively), i. e. Cryptic Philadelphia chromosome patients can be enrolled: * diagnosed within the past 3 months prior to D1 (i.e. within 60 days \[± 7 days\] since the date of first cytogenetic analysis), * in chronic phase defined by i) \<15 % blasts in peripheral blood and bone marrow, ii) \< 30% blast plus promyelocytes in peripheral blood and bone marrow; iii) \< 20 % basophils in peripheral blood and iv) ≥100 X 109 platelets/L in peripheral blood, * no extra-medullary disease. * All EUTOS long-term survival Scores. * No prior treatment for CML with any tyrosine kinase inhibitor (eg. imatinib, dasatinib, nilotinib or bosutinib), or busulphan; interferon-alpha; homoharringtonine; cytosine arabinoside; or any other investigational agent; with the exception of hydroxyurea and/or anagrelide which are the only authorized prior treatments. Note: Hydroxyurea should be stopped at least 24 hours prior the initiation of ponatinib. * Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1 or 2. * Adequate organ functions as defined below according to lab tests performed within 7 days before Day 1: Renal function: \- Serum creatinine clearance ≥ 50 mL/min/1.73m2 according to CKD-EPDI formula or serum creatinine ≤ 2 upper limit of normal (ULN). Hepatic function: * Serum bilirubin \< 1.5 × ULN, with the following exception: Patients with known Gilbert disease who have serum bilirubin level ≤ 3 ULN may be enrolled. * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤ 2.5 ULN. * Amylase or Lipase ≤ 1.5 × ULN Total cholesterol ≤1.5 ULN * Women of child-bearing potential must have a negative serum pregnancy test within 7 days before study drug start and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study treatments. * Fertile men must agree to use an effective method of contraception during the study and for up to 3 months after the last dose of study treatments. * Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol. * Patients must be covered by a medical insurance. Exclusion Criteria: * Any form of prior auto- or allo-hemopoietic stem cell transplant. * Hypersensitivity to the active substance or to any of the excipients of ponatinib and imatinib (see respective IB/SmPC). * Inability to take oral medication including malabsorption syndrome or other illness that could affect oral absorption of the study treatments (hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption). * Patients using, or requiring to use while on the study of any not permitted concomitant medications: * Any approved anti-cancer systemic treatment including chemotherapy, targeted therapy, immunotherapy or any biological therapy, * Any investigational agents, * Any treatment able to induce " torsades de pointes ", * Any strong inducers and inhibitors of CYP3A4. * Patients with a malignancy other than CP-CML within 5 years prior to Day 1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent). * Patients with active B or C hepatitis infection. Notes: Patients with past Hepatitis B Virus (HBV) infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen (HBsAg) test and a positive hepatitis B core antibody (HBcAb) test) are eligible. Patients with a positive HBcAb test must have a negative HBV DNA test at screening. Patients positive for Hepatitis C Virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. * Patients with significant cardiovascular disease, such as New York Heart Association cardiac disease Class II or greater, myocardial infarction within 3 months prior to D1, unstable arrhythmias, unstable angina, peripheral arterial occlusive disease, venous thromboembolism or pulmonary embolism, brain stroke, evolutive ischemic cardiopathy; prolonged corrected QT interval (QTc) interval on baseline electrocardiogram (\>450 msec on the Fridericia's correction) despite correction of predisposants factors; long congenital QT syndrome. * Any of the following medical conditions despite adequate therapeutic management: * Uncontrolled HTA despite adequate ongoing treatment. * Diabetes with documented target organ damage. * Pregnant or lactating women.