['philadelphia positive', 'bcr-abl positive', 'acute lymphoblastic leukemia']
['ponatinib']

        Inclusion Criteria:

          1. To be classified as having Ph+ ALL, patients must have >20% blasts in bone marrow at
             the time of diagnosis and no prior history of CML.

          2. Patients with previously untreated Ph+ and/or BCR/ABL + ALL:

               -  age ≥ 60 years old or

               -  age ≥ 18 years old, but unfit for program of intensive therapy and allogeneic SCT

          3. Adequate hepatic function as defined by the following criteria:

               -  total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's
                  syndrome

               -  alanine aminotransferase (ALT) ≤2.5 × ULN

               -  aspartate aminotransferase (AST) ≤2.5 × ULN.

          4. Adequate pancreatic function as defined by the following criterion:

             - serum lipase and amylase ≤1.5 × ULN.

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

          6. Female and male patients who are fertile must agree to use an effective form of
             contraception with their sexual partners from randomization through 4 months after the
             end of treatment.

          7. Signed written informed consent according to ICH/EU/GCP and national local laws.

        Exclusion Criteria:

          1. WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG).

          2. Active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubin ≥ 1.5 x ULN.

          3. History of acute pancreatitis within 1 year of study or history of chronic
             pancreatitis.

          4. History of alcohol abuse.

          5. Ongoing or active infections.

          6. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).

          7. Clinically significant, uncontrolled, or active cardiovascular disease, specifically
             including, but not restricted to:

               -  any history of myocardial infarction, stroke, or revascularization

               -  unstable angina or transient ischemic attack within 6 months prior to enrollment

               -  congestive heart failure within 6 months prior to enrollment, or left ventricular
                  ejection fraction (LVEF) less than lower limit of normal per local institutional
                  standards within 6 months prior to enrollment

               -  history of clinically significant (as determined by the treating physician)
                  atrial arrhythmia

               -  any history of ventricular arrhythmia

               -  any history of venous thromboembolism including deep venous thrombosis or
                  pulmonary embolism .

          8. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg).
             Patients with hypertension should be under treatment on study entry to effect blood
             pressure control.

          9. Taking medications that are known to be associated with Torsades de Pointes.

         10. Taking any medications or herbal supplements that are known to be strong inhibitors of
             CYP3A4 within at least 14 days before the first dose of ponatinib.

         11. Creatinine level > 2.5mg/dl or Glomerular Filtration Rate (GFR) < 20 ml/min or
             proteinuria > 3.5 g/day.

         12. Impairment of gastrointestinal (GI) function, or a GI disease that may significantly
             alter the absorption of study drugs (e.g. rare hereditary problems of galactose
             intolerance , the Lapp lactase deficiency or glucose-galactose malabsorption, severe
             malabsorption syndrome, or extended small bowel resection).

         13. Patients who are currently receiving treatment with any of the medications listed in
             Appendix E if the medications cannot be either discontinued or switched to a different
             medication prior to starting study drug. The medications listed in Appendix E have the
             potential to prolong QT.

         14. Patients who have received any investigational drug ≤ 4 weeks.

         15. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or
             who have not recovered from side effects of such therapy.

         16. Patients who are pregnant or breast feeding and adults of reproductive potential not
             employing an effective method of birth control (women of childbearing potential must
             have a negative serum pregnancy test within 48 hrs prior to administration of
             Ponatinib). Post menopausal women must be amenorrhoeic for at least 12 months to be
             considered of non-childbearing potential. Male and female patients must agree to
             employ an effective barrier method of birth control throughout the study and for up to
             4 months following discontinuation of study drugs.

         17. Patients with a history of another primary malignancy that is currently clinically
             significant or currently requires active intervention.

         18. Patients unwilling or unable to comply with the protocol.
      