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.
- 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.
- 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
- 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
- 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.