Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent according to ICH/EU/GCP and national local laws. 2. Newly diagnosed adult B-precursor Ph+ ALL patients. 3. WHO performance status less or equal to 2. 4. Age greater or equal to18 years, with no upper age limit. 5. Renal and hepatic function as defined below: - AST (GOT), ALT (GPT), and AP =65 years) yes F.1.3.1 Number of subjects for this age range 106
Exclusion criteria
Exclusion criteria: • History of or current relevant CNS pathology (ongoing 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 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 Ponatinib. - Angina pectoris. • Other clinically significant vascular and 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 Ponatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). • Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL). • Taking medications that are known to be associated with Torsades de Pointes and medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib. • 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 condition 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the efficacy of a front-line chemo-free strategy based on the administration of Ponatinib plus steroids as induction treatment, followed by the infusion of Blinatumomab as consolidation in adult Ph+ ALL (=18 years, no upper age limit), and to compare it with a chemotherapy scheme combined with Imatinib (control arm), in terms of event-free survival (EFS), a composite endpoint, with events defined as: non achievement of MRD negativity (CMR or PNQ), deaths for any reason, toxicity and resistance (due or not to an ABL1 mutation development) in adult Ph+ ALL (=18 years, no upper age limit).;Secondary Objective: 1.The key secondary objective is represented by the feasibility of patients’ stratification to allo-SCT allocation on the basis of a refined MRD evaluation and on the presence/absence of additional genetic lesions (namely IKZF1 plus CDKN2A/B and/or PAX5). 2.Capability of Blinatumomab to further reduce the MRD levels after Ponatinib induction. 3.CMR or positive not-quantifiable (PNQ) duration. 4.DFS at 1 and 3 years. 5.OS at 1 and 3 years. 6.Cumulative incidence of relapse (CIR). 7.Safety profile. 8.Comparison of patients’ quality of life (QoL) profiles over time by randomization arms. 9.CMR (or PNQ) achievement, duration of CMR, OS and DFS according to the clinical, biological and molecular characteristics at baseline, including type of fusion protein (p190 vs p210) and presence of additional genomic lesions. 10 & 11 please see the Protocol.;Primary end point(s): The primary endpoint of this study is to evaluate the efficacy of a sequential approach based on the administration of Ponatinib plus and Blinatumomab vs chemotherapy combined with Imatinib, in terms of (EFS), a composite endpoint, with events defined as: non achievement of MRD negativity (CMR or PNQ), deaths for any reason, toxicity and resistance (due or not to an ABL1 mutation development) in adult Ph+ ALL (=18 years, no upper age limit).;Timepoint(s) of evaluation of this e | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The feasibility of patients’ stratification to allo-SCT allocation on the basis of a refined MRD evaluation and on the presence/absence of IKZF1-plus). • Capability of Blinatumomab to further reduce the MRD levels after Ponatinib induction. • CMR or PNQ duration. • DFS at 1 and 3 years. • OS at 1 and 3 years. • CIR. • Safety profile. Safety profile in terms of incidence of grade =3 CTC-NCI side effects and toxicities. • Comparison of patients’ quality of life (QoL) profiles over time by randomization arms.;Timepoint(s) of evaluation of this end point: At 1and 3 years. | — |
Countries
Italy
Contacts
Public ContactCentro Dati
Fondazione GIMEMA Franco Mandelli Onlus
Outcome results
None listed