The study aims to verify the greater efficacy of the treatment of Acute Lymphoblastic Leukemia Ph + through the combination of Ponatinib and Blinatumomab, a specific monoclonal antibody, in adult patients, compared to the administration of chemotherapy and Imatinib.

Phase 1

• Conditions: Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.; MedDRA version: 21.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-006048-15-IT
• Lead Sponsor: FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-07
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 236

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 <2 x upper limit of normal (ULN).
- Total bilirubin <1.5 x ULN.
- Creatinine clearance equal or greater than 50 mL/min.
6.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.
7.Normal cardiac function.
8.No evidence of CNS leukemia at blinatumomab start.
9.Negative HIV test, negative hepatitis B (HBsAg) and hepatitis C virus (anti-HCV) test.
10.Negative pregnancy test in women of childbearing potential.
11.Bone marrow specimen from primary diagnosis available.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106

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 <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.
•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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified