Comparing locally produced CAR T-cells with commercial CAR T-cells for lymphoma treatment
A Phase II Non-inferiority Study Comparing Point-of-care Produced CAR T-cell to Commercial CAR T-cells in Patients with Relapsed/refractory Non-Hodgkin Lymphoma
This study is testing if locally made CAR T-cells can work better than commercially made ones for treating patients with tough cases of lymphoma.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 300 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University Medical Center Groningen Academic / other |
| Drugs / interventions | CAR T, Chimeric antigen receptor, immunotherapy |
| Locations | 7 sites (Amsterdam and 6 other locations) |
| Trial ID | NCT05641428 on ClinicalTrials.gov |
What this trial studies
This phase II, multi-center study evaluates the feasibility and clinical efficacy of locally manufactured CD19-directed CAR T-cells (ARI-0001) compared to commercially produced CAR T-cells, such as axicabtagene ciloleucel, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The trial addresses challenges associated with centralized production, including delays in treatment and potential quality degradation due to cryopreservation. By utilizing the CliniMACS Prodigy device for local manufacturing, the study aims to improve patient outcomes by providing timely and high-quality CAR T-cell therapy.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed DLBCL who have relapsed after at least two lines of systemic therapy.
Not a fit: Patients with significant central nervous system involvement or those who do not meet the inclusion criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could lead to more effective and accessible CAR T-cell therapies for patients with DLBCL.
How similar studies have performed: While CAR T-cell therapy has shown success in treating various hematological malignancies, this specific approach of local manufacturing is novel and has not been extensively tested in prior studies.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Amsterdam and 6 other locations
- NL-Amsterdam-AMC — Amsterdam, Netherlands (Recruiting)
- NL-Groningen-UMCG — Groningen, Netherlands (Recruiting)
- NL-Leiden-LUMC — Leiden, Netherlands (Recruiting)
- NL-Maastricht-MUMC — Maastricht, Netherlands (Recruiting)
- NL-Nijmegen-RADBOUDUMC — Nijmegen, Netherlands (Recruiting)
- NL-Rotterdam-ERASMUSMC — Rotterdam, Netherlands (Recruiting)
- NL-Utrecht-UMCUTRECHT — Utrecht, Netherlands (Recruiting)
Study contacts
- Principal investigator: T. (Tom) van Meerten — Umcg / Hovon
- Study coordinator: T. (Tom) van Meerten
- Email: hdc@erasmusmc.nl
- Phone: +31 (0)10 7041560
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.