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

NCT05641428 | Recruiting Phase 2 DMC

• 2 other identifiers: HO161 CAR T2021-000937-15
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 7

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.

Conditions

NHL; DLBCL - Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) from date of IMP infusion (if applicable)

  PFS from date of IMP infusion is defined as the time from IMP infusion, until progression, relapse or death from any cause, whichever comes first. PFS reflects tumor growth and, therefore, occurs prior to the endpoint of OS. Progression is defined as the first date of documentation of a new lesion or enlargement of a previous lesion, or the date of the scheduled clinic visit immediately after radiologic assessment has been completed. If there is missing information, censoring of the data may be defined as the last date at which progression status was adequately assessed.

  Approximately up to 60 months following first patient IMP infusion

Secondary Outcomes (22)

• Progression-free survival (PFS) from date of randomization

  Approximately up to 60 months following first patient enrollment

• Safety and toxicity assessment per AE reporting

  Approximately up to 60 months following first patient IMP infusion

• Overall Response Rate (ORR)

  At 4 weeks, 12 weeks, 6, 12 and 24 months after infusion of CAR T-cells

• Expansion of CAR T-cells

  Approximately up to 60 months following first patient IMP infusion

• Phenotype of CAR T-cells

  Approximately up to 60 months following first patient IMP infusion

Study Arms (2)

Arm A (ARI-0001)

EXPERIMENTAL

Infusion with Point of Care CAR T-cells

Drug: ARI-0001

Arm B (Axi-cel)

ACTIVE COMPARATOR

Infusion with Standard of Care CAR T-cells

Drug: Axi-cel

Interventions

ARI-0001 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 A (ARI-0001)

Axi-cel 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).

Arm B (Axi-cel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Stichting Hemato-Oncologie voor Volwassenen Nederland: collaborator

Study Sites (7)

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

Related Links

• Related Info

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• T. (Tom) van Meerten

  UMCG / HOVON

  PRINCIPAL INVESTIGATOR

Central Study Contacts

T. (Tom) van Meerten

CONTACT

+31 (0)10 7041560; hdc@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: December 7, 2022
• Study Start: October 18, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7)