VARNIMCABTAGENE AUTOLEUCEL for Diffuse large B-cell lymphoma (DLBCL) | Relapsed/refractory Non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- 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 refractory after 1st line systemic therapy or have a relapse after 12 months of finishing first line therapy or have R/R after at least 2 lines of systemic therapy"}
• {"criterion_text":"- Age ≥ 18 years."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Estimated life expectancy of >3 months other than primary disease."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Signed and dated informed consent before conduct of any trial-specific procedure."}
• {"criterion_text":"- Patient is capable of giving informed consent."}
• {"criterion_text":"- Approval by the Dutch CAR T-cell TumorBoard for lymphoma"}

Exclusion criteria

• {"criterion_text":"- Absolute neutrophil count (ANC) <1.0x109/L."}
• {"criterion_text":"- Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease."}
• {"criterion_text":"- Active systemic autoimmune disease for which immunnosupressive therapy is required."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Active systemic fungal, viral or bacterial infection."}
• {"criterion_text":"- Clinical heart failure with New York Heart Association class ≥2 or Left Ventricular Ejection Fraction (LVEF) <40%."}
• {"criterion_text":"- Resting oxygen saturation <92% on room air."}
• {"criterion_text":"- Liver dysfunction as indicated by total bilirubin, AST and/or ALT >5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert disease."}
• {"criterion_text":"- GFR <40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection."}
• {"criterion_text":"- Pregnant or breast-feeding woman."}
• {"criterion_text":"- Active other malignancy requiring treatment."}
• {"criterion_text":"- Platelet count <50x109/L."}
• {"criterion_text":"- Medical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolone <10 mg/day."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule."}
• {"criterion_text":"- Absolute lymphocyte count <0.1x109/L."}
• {"criterion_text":"- Primary CNS lymphoma."}
• {"criterion_text":"- Known history of infection with hepatitis C or B virus unless treated and confirmed to be polymerase chain reaction (PCR) negative."}
• {"criterion_text":"- Active HIV infection with detectable viral load or CD4 T-cell count below 0.20x109/L."}
• {"criterion_text":"- Known history or presence of seizure activities or on active anti- seizure medications within the previous 12 months."}
• {"criterion_text":"- Known history of CVA within prior 12 months."}
• {"criterion_text":"- Unstable neurological deficits."}

Primary endpoints

• {"endpoint_text":"- PFS from date of IMP infusion (if applicable).","definition_or_measurement_approach":"Progression-free survival measured from date of investigational medicinal product (IMP) infusion (if applicable)."}

Secondary endpoints

• {"endpoint_text":"- PFS from date of randomization.","definition_or_measurement_approach":"Progression-free survival measured from date of randomization."}
• {"endpoint_text":"- Safety and toxicity assessment of ARI-0001 CAR T-cells and Axi-cel per AE reporting classified according to CTCAE Version 5 and CRS and ICANS classified according to the ASTCT criteria.","definition_or_measurement_approach":"Adverse events reported and classified per CTCAE v5; CRS and ICANS graded per ASTCT criteria."}
• {"endpoint_text":"- Overall response rate (ORR, sum of complete response [CR] and partial response [PR]), as well as CR, PR, SD and PD/relapse at 4 weeks, 12 weeks, 6, 12 and 24 months after infusion of CAR T-cells.","definition_or_measurement_approach":"Response assessments (ORR, CR, PR, SD, PD/relapse) at specified timepoints: 4 weeks, 12 weeks, 6, 12 and 24 months post-infusion."}
• {"endpoint_text":"- Expansion, phenotype and persistence of ARI-0001 CAR T-cells in both treatment arms.","definition_or_measurement_approach":"Laboratory/immune monitoring of CAR T-cell expansion, phenotype and persistence in both arms."}
• {"endpoint_text":"- Best overall response (BOR) rate at 4 weeks, 12 weeks, 6, 12 and 24 months after infusion of CAR T-cells.","definition_or_measurement_approach":"Best overall response evaluated at specified timepoints post-infusion."}
• {"endpoint_text":"- Duration of response (DOR).","definition_or_measurement_approach":"Time from documented response to progression or relapse."}
• {"endpoint_text":"- OS from date of randomization, and from date of CAR T-cell infusion (if applicable).","definition_or_measurement_approach":"Overall survival measured from randomization and from CAR T-cell infusion (if applicable)."}
• {"endpoint_text":"- Patient Reported Outcome/Quality of Life (PRO/QOL).","definition_or_measurement_approach":"PRO/QoL assessed using patient questionnaires (documented patient-facing QoL questionnaires present)."}
• {"endpoint_text":"- CAR T-cell expansion, persistence, and T-cell characteristics in both treatment arms (ARI-0001 vs Axi-cel).","definition_or_measurement_approach":"Assessment of CAR T-cell expansion, persistence and T-cell characteristics by immunologic assays."}
• {"endpoint_text":"- PoC CAR T-cell production characteristics (e.g. number of viable T-cells, transduction efficiency, T-cell subsets (activated T-cells, memory T-cells)), including the functional characteristics (e.g. potency tests) between the different production sites.","definition_or_measurement_approach":"Manufacturing and quality metrics of PoC CAR T-cell products across production sites (viable T-cell counts, transduction efficiency, subsets, potency tests)."}
• {"endpoint_text":"- The association of the functional characteristics (e.g. potency tests) of the CAR T-cell products (ARI-0001 CAR T-cells) with CAR T-cell expansion, persistence, adverse events, response rates and progression free survival.","definition_or_measurement_approach":"Correlative analyses linking product functional characteristics to clinical and immunologic outcomes."}
• {"endpoint_text":"- Proportion of successful batches between the different production sites.","definition_or_measurement_approach":"Proportion of manufacturing batches meeting predefined success criteria per site."}
• {"endpoint_text":"- Number of days between leukapheresis and infusion of CAR T-cells (vein-to-vein time).","definition_or_measurement_approach":"Measurement of time (days) from leukapheresis to CAR T-cell infusion (vein-to-vein time)."}
• {"endpoint_text":"- Fludarabine pharmacokinetics.","definition_or_measurement_approach":"Pharmacokinetic analysis of fludarabine."}

Netherlands

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

22-05-2025

Processing Time Days

275

Number Of Sites

8

Number Of Participants

340

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Netherlands","full_name":"Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting","duties_or_roles":"codes: 1,10,12,3,5,6,7,8","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Radboud universitair medisch centrum Stichting","duties_or_roles":"codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Groningen","duties_or_roles":"codes: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Netherlands","full_name":"Universitair Medisch Centrum Groningen","duties_or_roles":"code: 15 (manufactering ARI-0001 CAR T-cells)","organisation_type":"Hospital/Clinic/Other health care facility"}