This study aims at exploring the activity of a frontline approach based on dasatinib plus steroids administration as induction treatment, followed by the infusion of Blinatumomab, in adult Ph+ ALL.

Inclusion Criteria:

• Newly diagnosed adult B-precursor Ph+ ALL patients.

• Age greater or equal to18 years,

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

• ECOG Performance Status 0 or 1 and/or WHO performance status less or equal to 2.

• Renal and hepatic function as defined below:

  • AST (GOT), ALT (GPT), and AP <2 x upper limit of normal (ULN).
  • Total bilirubin <1.5 x ULN.
  • Creatinine clearance equal or greater than 50 mL/min.

• Pancreatic function as defined below:

  • Serum amylase less or equal to 1.5 x ULN
  • Serum lipase less or equal to1.5 x ULN.

• Normal cardiac function.

• Negative HIV test, negative HBV DNA and HCV RNA.

• Negative pregnancy test in women of childbearing potential.

• Bone marrow specimen from primary diagnosis available.

Exclusion Criteria:

• History of or current relevant CNS pathology (current ≥grade 2 epilepsy, seizure, paresis, aphasia, clinically relevant apoplexia, severe brain injuries, dementia, Parkinson's disease, organic brain syndrome, psychosis).

• Impaired cardiac function, including any one of the following:

  • LVEF <45% as determined by MUGA scan or echocardiogram.
  • Complete left bundle branch block.
  • Use of a cardiac pacemaker.
  • ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads.
  • Congenital long QT syndrome.
  • History of or presence of significant ventricular or atrial arrhythmia.
  • Clinically significant resting bradycardia (<50 beats per minute).
  • QTc >450 msec on screening ECG (using the QTcF formula).
  • Right bundle branch block plus left anterior hemiblock, bifascicular block.
  • Myocardial infarction within 3 months prior to starting Dasatinib.
  • Angina pectoris.

• Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dasatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

• History of or current autoimmune disease.

• Systemic cancer chemotherapy within 2 weeks prior to study.

• Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation.

• Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix.

• Active infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the study as judged by the investigator.

• Nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter.