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

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

NCT ID: NCT05641428

Condition: NHL
DLBCL - Diffuse Large B Cell Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ARI-0001
Description: Infusion with a single target dose of 2.0 x 10^6 Point of Care CAR T-cells/kg BW (range 1 -2.0x 10^6 CAR T-cells /kg BW).
Arm group label: Arm A (ARI-0001)

Intervention type: Drug
Intervention name: Axi-cel
Description: Infusion with a single target dose of 2.0 x 10^6 Standard of Care CAR T-cells/kg BW (range 1 -2.0x 10^6 CAR T-cells /kg BW).
Arm group label: Arm B (Axi-cel)

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.

Detailed description: Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of adoptive cell therapy that has proven its efficacy in the treatment of various hematological malignancies, including B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL). CD19 has been the most studied target antigen for CAR T-cell immunotherapy. Anti-CD19 CAR T-cell therapy has shown durable responses in patients with different B-NHLs, including Diffuse Large B-cell Lymphoma (DLBCL). Unfortunately, up to 50-60% of the patients do not respond to CD19-directed CAR T-cell therapy or relapse. There are several shortcomings of current CD19-directed CAR T-cell therapy, that are likely responsible for therapy failure, namely: i) Due to centralized production at commercial sites, the production is time consuming (about 4 weeks), meaning that patients with rapidly progressive lymphoma may not reach the moment of the infusion of the anti-CD19 CAR T-cells. ii) Furthermore, for the current production processes, the autologous T-cells need to be cryopreserved for shipment from the hospital to the production sites and vice versa. This (double) cryopreservation process can decrease the quality of the CAR T-cells. This trial aims to address these shortcomings and will study the feasibility, and clinical efficacy of local manufacturing of CD19-directed CAR T-cells (ARI-0001 CAR T-cells), in a completely closed system using the CliniMACS Prodigy device. This study will compare the clinical efficacy of locally produced CAR T-cells to 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. This in-house (point-of-care) production process of ARI-0001 will take approximately 7-12 days and thus will generate CAR T-cells "faster" which will be infused in the patient without cryopreservation ("fresh", of note, a back-up cryopreserved product will also be manufactured). Furthermore, the point-of-care production process can be replicated in academic institutions with the appropriate cellular manufacturing facilities. If successful, this study will show feasibility of local production of CAR T-cell therapy, improving their rapid accessibility and quality.

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: NL-Amsterdam-AMC

Address:
City: Amsterdam
Country: Netherlands

Status: Recruiting

Facility:
Name: NL-Groningen-UMCG

Address:
City: Groningen
Country: Netherlands

Status: Recruiting

Facility:
Name: NL-Leiden-LUMC

Address:
City: Leiden
Country: Netherlands

Status: Recruiting

Facility:
Name: NL-Maastricht-MUMC

Address:
City: Maastricht
Country: Netherlands

Status: Recruiting

Facility:
Name: NL-Nijmegen-RADBOUDUMC

Address:
City: Nijmegen
Country: Netherlands

Status: Recruiting

Facility:
Name: NL-Rotterdam-ERASMUSMC

Address:
City: Rotterdam
Country: Netherlands

Status: Recruiting

Facility:
Name: NL-Utrecht-UMCUTRECHT

Address:
City: Utrecht
Country: Netherlands

Status: Recruiting

Start date: October 18, 2022

Completion date: December 2027

Lead sponsor:
Agency: University Medical Center Groningen
Agency class: Other

Collaborator:
Agency: Stichting Hemato-Oncologie voor Volwassenen Nederland
Agency class: Other

Source: University Medical Center Groningen

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05641428
http://www.hovon.nl