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

NCT ID: NCT05641428

Last Updated: 2024-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-18
• Study Completion Date: 2027-12-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (ARI-0001)

Infusion with Point of Care CAR T-cells

Group Type: EXPERIMENTAL

ARI-0001

Intervention Type: DRUG

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 B (Axi-cel)

Infusion with Standard of Care CAR T-cells

Group Type: ACTIVE_COMPARATOR

Axi-cel

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stichting Hemato-Oncologie voor Volwassenen Nederland

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

T. (Tom) van Meerten

Role: PRINCIPAL_INVESTIGATOR

UMCG / HOVON

Locations

NL-Amsterdam-AMC

Amsterdam, , Netherlands

Site Status: RECRUITING

NL-Groningen-UMCG

Groningen, , Netherlands

Site Status: RECRUITING

NL-Leiden-LUMC

Leiden, , Netherlands

Site Status: RECRUITING

NL-Maastricht-MUMC

Maastricht, , Netherlands

Site Status: RECRUITING

NL-Nijmegen-RADBOUDUMC

Nijmegen, , Netherlands

Site Status: RECRUITING

NL-Rotterdam-ERASMUSMC

Rotterdam, , Netherlands

Site Status: RECRUITING

NL-Utrecht-UMCUTRECHT

Utrecht, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

T. (Tom) van Meerten

Role: CONTACT

hdc@erasmusmc.nl

+31 (0)10 7041560

Related Links

http://www.hovon.nl

Related Info

Other Identifiers

2021-000937-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HO161 CAR T

Identifier Type: -

Identifier Source: org_study_id