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

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.

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 therapyAge ≥ 18 and ≤80 yearsEastern 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 haveNo signs or symptoms of CNS involvementNo 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 cellsEstimated life expectancy of >3 months other than primary diseasePatients 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 regimenSigned and dated informed consent before conduct of any trial-specific procedurePatient is capable of giving informed consentExclusion Criteria:Absolute neutrophil count (ANC) <1.0x109/LPlatelet count <50x109/LAbsolute lymphocyte count <0.1x109/LPrimary CNS lymphomaKnown history of infection with hepatitis C or B virus unless treated and confirmed to be polymerase chain reaction (PCR) negativeHIV infectionKnown history or presence of seizure activities or on active anti- seizure medications within the previous 12 monthsKnown history of CVA within prior 12 monthsUnstable neurological deficitsKnown history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory diseaseActive systemic autoimmune disease for which immunosupressive therapy is requiredPresence 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 baselineActive systemic fungal, viral or bacterial infectionClinical heart failure with New York Heart Association class ≥2 (appendix F) or Left Ventricular Ejection Fraction (LVEF) <40%Resting oxygen saturation <92% on room airLiver dysfunction as indicated by total bilirubin, AST and/or ALT >5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert diseaseGFR <40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collectionPregnant or breast-feeding womanActive other malignancy requiring treatmentMedical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolone <10 mg/dayHistory 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 toxicitiesAny psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule