Newly Diagnosed Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Sequential Treatment with Ponatinib and the Bispecific Monoclonal Antibody Blinatumomab vs Chemotherapy and Imatinib. ALL2820

Fondazione Gimema Franco Mandelli Onlus77 sites in 1 country236 target enrollmentOctober 1, 2024

DrugsMETHYLPREDNISOLONE SODIUM SUCCINATE, METHYLPREDNISOLONE SODIUM SUCCINATE METHOTREXATE FILGRASTIM MEDI-538 MT103 Benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-BLINCYTO 38.5 micrograms powder for concentrate and solution for solution for infusion CYCLOPHOSPHAMIDE 3-(2-(IMIDAZO(1,2-B)PYRIDAZIN-3-YL)ETHYNYL)-4-METHYL-N-(4-((4-METHYLPIPERAZIN-1- YL)METHYL)-3-(TRIFLUOROMETHYL)PHENYL)BENZAMIDE METHYLPREDNISOLONE SODIUM SUCCINATE Vincristine Sulfate 1 mg/ml solution for injection CYTARABINE PREDNISONE, PREDNISONE LEDERFOLIN 25 mg Polvere per soluzione iniettabile per uso endovenoso Dexamethasone Phosphate 4 mg/ml Solution for Injection CYTARABINE, CYTARABINE, CYTARABINE Melphalan 50 mg powder and solvent for solution for injection/infusion CALCIUM (2R)-2-[[4-[[(6S)-2-AMINO-5-FORMYL-4-OXO-1,6,7,8-TETRAHYDROPTERIDIN-6-YL]METHYLAMINO]BENZOYL]AMINO]PENTANEDIOATE AP-24534 Keppra 250 mg film-coated tablets Idarubicina Sandoz 1 mg/ml concentrato per soluzione per infusione Iclusig 15 mg film-coated tablets PURINETHOL 50 mg compresse RECOMBINANT ANTIBODY DERIVATIVE AGAINST HUMAN CD19 AND CD3 Glivec 100 mg hard capsules PREDNISONE Levoleucovorin calcium MT-103 METHOTREXATE, METHOTREXATE, METHOTREXATE

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Not specified
Sponsor: Fondazione Gimema Franco Mandelli Onlus
Enrollment: 236
Locations: 77
Primary Endpoint: 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).
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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).

Registry

euclinicaltrials.eu

Start Date

October 1, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Responsible Party

Principal Investigator

GIMEMA Centro Dati

Scientific

Fondazione Gimema Franco Mandelli Onlus

Eligibility Criteria

Inclusion Criteria

•Signed written informed consent according to ICH/EU/GCP and national local laws.
•Negative pregnancy test in women of childbearing potential.
•Bone marrow specimen from primary diagnosis available.
•Newly diagnosed adult B-precursor Ph+ ALL patients.
•WHO performance status less or equal to
•Age greater or equal to18 years, with no upper age limit.
•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 and serum lipase less or equal to1.5 x ULN.
•Normal cardiac function.
•No evidence of CNS leukemia at blinatumomab start.

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).
•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.
•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 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.

Outcomes

Primary Outcomes

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).

Secondary Outcomes

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.
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.
Comparison of patients’ quality of life (QoL) profiles over time by randomization arms.