Is Trogocytosis a Predictive Marker of CAR-T Cell Response in Diffuse Large B-cell Lymphoma?

NCT ID: NCT06352242

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-22
• Study Completion Date: 2026-05-22

Brief Summary

CAR-T cell therapy has improved survival in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL R/R). However, only 65% of patients achieve a complete metabolic response after this treatment. To date, there is no predictive test for therapeutic response after injection of CAR-T cells. Recent studies have shown that the level of trogocytosis by immune cells correlates with the persistence of tumor cells in patients with hematological malignancies. Our main objective is to identify a phenotypic "signature" of trogocytosis predictive of therapeutic response 6 months after injection of CAR-T cells for DLBCL.

Detailed Description

The therapeutic use of CAR-T cells (Chimeric Antigen Receptor T-cells) has significantly improved the survival of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, only 65% of patients achieve metabolic complete response after this treatment, and one year after CAR-T cells infusion, between 50 and 60% of patients have relapsed or died. Injection of CAR-T cells can also be responsible for serious immunologic and hematologic adverse events. To date, there is no predictive test for the therapeutic response or toxicity following injection of CAR-T cells.

Trogocytosis is a physiological mechanism by which an effector immune cell integrates fragments of the membrane of target cells into its membrane. These aberrant membrane markers can directly modify the functions of the cell that has acquired them. Although the physiological role of trogocytosis remains debated, recent studies have shown that the level of trogocytosis in immune effector cells is correlated with persistent tumor cells in patients with hematological malignancies.

Our main hypothesis is that, in DLBCL, the level of early trogocytosis, assessed by the aberrant expression of tumor markers on the surface of CAR-T cells and other immune effector cells between D0 and D30 after CAR-T cells infusion, correlates with therapeutic response at M6 and/or the occurrence of immunological or severe hematological CAR-T cells side-effects.

Conditions

Diffuse Large B Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Patients

Blood sample for Flow cytometry analysis

Group Type: OTHER

Flow cytometry analysis to determine the level of trogocytosis by effector immune cells in patients

Intervention Type: OTHER

For each patient, a blood sample will be taken at D0 before the CAR-T cells are injected then at D3, D7, D10, D30 after the injection. Flow cytometry analysis will be performed on each sample on the day of collection to determine the level of trogocytosis by effector immune cells (T lymphocytes, NK cells, CAR-T cells) and to define the phenotypic "signature" of trogocytosis.

healthy volunteer donor

Blood sample for Flow cytometry analysis

Group Type: OTHER

Flow cytometry analysis to determine the level of trogocytosis by effector immune cells in volunteers

Intervention Type: OTHER

For each healthy volunteer, a single blood sample will be taken at enrollment. Flow cytometry analysis will be performed on each sample on the day of collection to determine the level of trogocytosis of normal lymphocytes and NK cells.

Interventions

Flow cytometry analysis to determine the level of trogocytosis by effector immune cells in patients

For each patient, a blood sample will be taken at D0 before the CAR-T cells are injected then at D3, D7, D10, D30 after the injection. Flow cytometry analysis will be performed on each sample on the day of collection to determine the level of trogocytosis by effector immune cells (T lymphocytes, NK cells, CAR-T cells) and to define the phenotypic "signature" of trogocytosis.

Intervention Type: OTHER

Flow cytometry analysis to determine the level of trogocytosis by effector immune cells in volunteers

For each healthy volunteer, a single blood sample will be taken at enrollment. Flow cytometry analysis will be performed on each sample on the day of collection to determine the level of trogocytosis of normal lymphocytes and NK cells.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• For patients

• Patient who has given free and informed consent in writing for inclusion in the non-interventional CART-BANK protocol, and orally for the CARTROG protocol,
• Patients over 18 years of age at the time of inclusion,
• Diagnosis of LDGCB,
• Decision to treat with anti-CD19 CAR-T cells,
• Patient affiliated to or benefiting from a social security scheme.
• For healthy volunteers:

• Given free and informed oral consent for inclusion in the CARTROG protocol,
• Donor between 18 and 70 years of age at the time of inclusion,
• No history of solid cancer or hematological malignancy,
• No known chronic pathology (e.g. hypertension, diabetes, etc.) and no daily treatment,
• No surgical treatment within the last 6 months.

• Pregnant or breast-feeding patient,
• Patient unable to follow the procedures and/or frequency of visits planned in the trial, for psychological, family, social or geographical reasons,
• Patient unable to consent freely to inclusion, under guardianship, curatorship or safeguard of justice.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ludovic GABELLIER, MD

Role: PRINCIPAL_INVESTIGATOR

Montpellier University Hospital

Florence GALTIER, MD

Role: PRINCIPAL_INVESTIGATOR

Montpellier University Hospital

Locations

Clinical hematology department, University Hospital

Montpellier, , France

Site Status: RECRUITING

Clinical Investigation Center, University Hospital

Montpellier, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Valérie ROUILLE

Role: CONTACT

v-rouille@chu-montpellier.fr

+33467332645

Facility Contacts

Valérie ROUILLE

Role: primary

v-rouille@chu-montpellier.fr

Philippe GERAUD

Role: primary

p-geraud@chu-montpellier.fr

+33467332324

Other Identifiers

2024-A00508-39

Identifier Type: REGISTRY

Identifier Source: secondary_id

RECHMPL24_0076

Identifier Type: -

Identifier Source: org_study_id