Ponatinib in Adult Ph+ ALL Patients With MRD Positivity or Hematological Relapse

Inclusion Criteria: 1. Ph+ ALL patients with evidence of MRD disease or in hematologic and extra-hematologic relapse/refractoriness after any previous treatment, will be considered eligible to enter the study. 2. Age ≥18 years old with no upper age limit. 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 enrollment. 6. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment 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. Uncontrolled active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubine ≥ 1.5 x ULN not due to the disease. 3. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis. 4. History of alcohol abuse. 5. Ongoing or active uncontrolled 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 * 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. 8. Taking medications that are known to be associated with Torsades de Pointes. 9. 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. 10. Creatinine level \>2.5mg/dl or glomerular filtration rate (GFR) \<20 ml/min or proteinuria \>3.5 g/day. 11. 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.