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

• Status: Recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

A phase II, multi-center study to compare the feasibility, and clinical efficacy of local manufacturing of CD19-directed CAR T-cells (ARI-0001 CAR T-cells) with commercial produced CAR T-cells (for example axicabtagene ciloleucel, a CD19 targeting commercially available CAR T-cell) in patients with relapsed or refractory (R/R) DLBCL.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Medical Center Groningen
• Collaborator: Stichting Hemato-Oncologie voor Volwassenen Nederland

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 and ≤80 years

• Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2 (appendix D)

• If the patient has a history of central nervous system (CNS) involvement, then he/she must have

• No signs or symptoms of CNS involvement

• No active disease on magnetic resonance imaging (MRI)

• Absence of large cell lymphoma in cerebral spinal fluid (CSF) on cytospin preparation or flow cytometry, regardless of the number of white blood cells

• 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) <1.0x109/L

• Platelet count <50x109/L

• Absolute lymphocyte count <0.1x109/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

• HIV infection

• 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