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 2 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 or triglycerides ≤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.