Acute Lymphoblastic Leukemia Philadelphia Chromosome Positive (Ph+) MedDRA version: 21.0 Level: LLT Classification code 10000844 Term: Acute lymphoblastic leukaemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: SPRYCEL - 140 MG-COMPRESSA RIVESTITA CON FILM-USO ORALE-BLISTER DIVISIBILE PER DOSE UNITARIA30X1 COMPRESSE
Product Name: Sprycel
Product Code: [NA]
Pharmaceutical Form: Film-coated table
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Newly diagnosed adult B-precursor Ph+ ALL patients. 2) Age greater or equal to18 years. 3) Signed written informed consent according to ICH/EU/GCP and national local laws. 4) ECOG Performance Status 0 or 1 and/or WHO performance status less or equal to 2. 5) Renal and hepatic function as defined below: o AST (GOT), ALT (GPT), and AP =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1) Prior systemic chemotherapy for leukemia and/or CD19-directed therapy 2) 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). 3) Impaired cardiac function, including any one of the following: -LVEF (Left Ventricular Ejection Fraction) 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 (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. 4) 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). 5) 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). 6) History of or current autoimmune disease. 7) Systemic cancer chemotherapy within 2 weeks prior to study. 8) Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation. 9) 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. 10) Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator. 11) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the activity of a combination approach based on dasatinib and blinatumomab in obtaining a minimal residual disease MRD negativity (complete molecular response: CMR, e.g. BCR-ABL1/ABL1=0) in adult Ph+ ALL.;Secondary Objective: 1) The feasibility of a chemo-free approach, based on Dasatinib and Blinatumomab, in adult Ph+ ALL patients =18 years, with no upper age limit 2) CMR achievement after induction with Dasatinib 3) Capability of Blinatumomab to reduce the MRD levels (an extension of the primary objective) 4) CMR duration 5) Disease-free survival (DFS) 6) Overall survival (OS) 7) Cumulative incidence of relapse (CIR) 8) Safety profile 9) CMR achievement, duration of CMR, OS and DFS according to the clinical, biological and molecular characteristics: clinical and biological assessment at baseline, type of fusion protein (p190 vs p210) and presence of additional genomic lesions identified by SNP arrays.;Primary end point(s): The rate of patients who achieve MRD negativity (CMR) upon treatment, in particular: the rate of patients in CMR after 2 cycles of Blinatumomab.;Timepoint(s) of evaluation of this end point: Interim analysis will be performed after the first stage (29 evaluable patients) and at the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Feasibility, calculated on the rate of patients completing the 2 cycles of Blinatumomab treatment and alive in first CHR from day +85 at 12 months 2)Rate of patients in CMR at day +22, +45, +57 and +85 3) CMR duration 4) DFS 5) OS 6) CIR 7) Safety profile in terms of incidence of grade >3 CTC-NCI side effects and toxicities. 8) Role of clinical and biological assessment at baseline, type of fusion protein (p190 vs p210) and presence of additional genomic lesions identified by SNP arrays on CMR achievement, duration of CMR, OS and DFS.;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Countries
Italy
Contacts
Public ContactCentro dati
Fondazione G.I.M.EM.A Franco Mandelli ONLUS
Outcome results
None listed