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

4. Effective contraception.

Exclusion Criteria:

1. Uncontrolled congestive heart failure or/and uncontrolled hypertension.

2. History of myocardial infarction within 3 months, or uncontrolled angina pectoris.

3. Significant electric heart abnormalities, including history or presence of
significant ventricular or atrial tachyarrhythmias, congenital long QT syndrome
and/or QTc > 450 msec on screening ECG (using the QTcF formula) .

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

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

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

7. History of acute pancreatitis within 1 year of study, or history of chronic
pancreatitis, history of alcohol abuse; ongoing or active infection; uncontrolled
hypertriglyceridemia (triglicerides > 450 mg/dL).

8. Impairment of gastrointestinal (GI) function, or a GI disease that may significantly
alter the absorption of study drugs (e.g., severe malabsorption syndrome, or extended
small bowel resection).

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

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

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

12. 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 amenorrhoic 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 3 months following discontinuation of study drugs.

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

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