D-ALBA Frontline Sequential Dasatinib and Blinatumomab in Adult Philadelphia Positive Acute Lymphoblastic Leukemia

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.


Eligibility Criteria:
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.