NCT05641428

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• NHL
• DLBCL - Diffuse Large B Cell Lymphoma

Interventions

Type	Name	Description
DRUG	ARI-0001	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).
DRUG	Axi-cel	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).

Timeline

• Start date: 2022-10-18
• Primary completion: 2025-12-01
• Completion: 2027-12-01
• First posted: 2022-12-07
• Last updated: 2024-09-23

Locations

7 sites across 1 country: Netherlands