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

NCT06352242 | Recruiting

• 2 other identifiers: RECHMPL24_00762024-A00508-39
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

lymphoma; chimeric antigen receptor T-cell; trogocytosis; prognosis

Outcome Measures

Primary Outcomes (1)

• Identification of a phenotypic "signature" of trogocytosis predictive of failure to achieve a complete metabolic response for patients with diffuse large B-cell lymphoma.

  Using flow cytometry to determine the level of trogocytosis, the phenotypic "signature" of trogocytosis will be assessed by the AUC : area under the ROC (Receiver operating characteristic) curve; established on circulating CAR-T cells, T lymphocytes and NK cells of patients, and defined as: the percentage of cells aberrantly expressing different tumor antigens normally expressed on lymphoma cells (CD19, CD20, etc.) at the different analysis times and/or the median florescence intensity (MFI) of the expression of these markers at the different analysis times and/or the evolution of these percentages and the MFI between 2 analysis times. Failure to obtain a complete metabolic response will be defined by: the absence of a complete metabolic response on the PET scans of D30, D90 and M6 in the absence of implementation of a new therapeutic line; or by the absence of complete metabolic response on all PET scans carried out before the implementation of a new therapeutic line.

  During 6 months after CAR-T cells injection

Secondary Outcomes (3)

• Identification of a phenotypic "signature" of trogocytosis predictive of the occurrence of grade II or more immunological adverse events

  During 60 days after CAR-T cells injection

• Identification of a phenotypic "signature" of trogocytosis predictive of the occurrence of serious hematological side effects.

  Between Day 30 and 6 months after CAR-T cells injection

• Determination of the trogocytosis level of normal lymphocytes and NK cells in healthy subjects

  At enrollment

Study Arms (2)

Patients

OTHER

Blood sample for Flow cytometry analysis

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

healthy volunteer donor

OTHER

Blood sample for Flow cytometry analysis

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

Interventions

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

Patients

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

healthy volunteer donor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For patients
• 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:
• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (2)

Clinical hematology department, University Hospital

Montpellier, France

RECRUITING

Clinical Investigation Center, University Hospital

Montpellier, France

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ludovic GABELLIER, MD

  Montpellier University Hospital

  PRINCIPAL INVESTIGATOR

• Florence GALTIER, MD

  Montpellier University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valérie ROUILLE

CONTACT

+33467332645; v-rouille@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: April 8, 2024
• Study Start: May 22, 2024
• Primary Completion: May 22, 2026
• Study Completion: May 22, 2026
• Last Updated: September 30, 2025

Record last verified: 2025-01

Locations

FR (2)