Comparison of Point-of-care Produced CAR T-cell with Commercial CAR T-cells in Patients with R/R LBCL

Launched by UNIVERSITY MEDICAL CENTER GRONINGEN · Nov 30, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new way to produce CAR T-cells, which are a type of treatment for certain blood cancers like relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In this trial, researchers want to see if CAR T-cells made locally at the treatment center (called ARI-0001) are just as effective and feasible as the commercially available CAR T-cells that patients currently receive. The goal is to find a method that could be easier and quicker for patients.

To be eligible for this study, participants must be at least 18 years old and have been diagnosed with DLBCL or specific related types of lymphoma. They should also have had at least two previous treatments that did not work. Participants will need to provide informed consent, which means they understand the study and agree to take part. Throughout the trial, patients can expect to receive close monitoring and care from healthcare professionals to ensure their safety and the effectiveness of the treatment. It's important to know that there are certain health conditions that might exclude someone from participating, so discussing health history with the medical team is vital.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, T-cell/histocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, transformed lymphoma (transformed follicular) and R/R after at least 2 lines of systemic therapy
• • Age ≥ 18
• • Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2
• • Secondary central nervous system (CNS) involvement is allowed however, then he/she must have
• • \* No signs or symptoms of CNS involvement that would hamper adequate ICANS assessment
• • Estimated life expectancy of \>3 months other than primary disease
• • Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen
• • Signed and dated informed consent before conduct of any trial-specific procedure
• • Patient is capable of giving informed consent
• Exclusion Criteria:
• • Absolute neutrophil count (ANC) \<1.0x10\^9/L
• • Platelet count \<50x10\^9/L
• • Absolute lymphocyte count \<0.1x10\^9/L
• • Primary CNS lymphoma
• • Known history of infection with hepatitis C or B virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
• • Active HIV infection with detectable viral load or CD4 T-cell count below 0.20x10\^9/L
• • Known history or presence of seizure activities or on active anti- seizure medications within the previous 12 months
• • Known history of CVA within prior 12 months
• • Unstable neurological deficits
• • Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease
• • Active systemic autoimmune disease for which immunosupressive therapy is required
• • Presence of CNS disease that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity, baseline dementia that would interfere with therapy or monitoring, determined using mini-mental status exam at baseline
• • Active systemic fungal, viral or bacterial infection
• • Clinical heart failure with New York Heart Association class ≥2 (appendix F) or Left Ventricular Ejection Fraction (LVEF) \<40%
• • Resting oxygen saturation \<92% on room air
• • Liver dysfunction as indicated by total bilirubin, AST and/or ALT \>5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert disease
• • GFR \<40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection
• • Pregnant or breast-feeding woman
• • Active other malignancy requiring treatment
• • Medical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolone \<10 mg/day
• • History of severe immediate hypersensitivity reaction against any drug or its Ingredients/impurities that is scheduled to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, premedication for infusion, or rescue medication/salvage therapies for treatment related toxicities
• • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule