Study of the Hematopoietic Niche and the Role of Inflammation in the Pathophysiology of Cytopenias After CAR-T Cell Therapy: Potential of Therapies Directed to Repair the Bone Marrow Microenvironment

NCT06439173 | Recruiting

• 2 other identifiers: PI23/01107PI2024 03 1552
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Immunotherapy with chimeric antigen receptor T-cells (CAR-T) has revolutionized the treatment of oncohematological diseases and its applications in solid tumors and non-neoplastic diseases are advancing. Cytopenias after CAR-T therapy are the most frequent complication in the medium and long term after treatment, they are a cause of morbimortality, and there are no effective therapies available. The general objective of the present research project is to analyze, in a series of 40 patients with diffuse large B-cell lymphoma undergoing consecutive commercial CAR-T therapy at the University Hospital of Salamanca, the characteristics of the hematopoietic niche and the systemic and bone marrow inflammatory status in patients with prolonged cytopenias after CAR-T cell therapy with respect to those without cytopenias and with respect to the pre-treatment situation (performing quantitative and functional analysis of the stroma by immunohistochemistry, flow cytometry and genomic studies, in addition to functional hematopoietic assays-clonogenic assays, long-term cultures-), and to evaluate both in vitro (by co-culturing with macrophages activated by CAR-T/tumor cell interaction and assessing cytokines) and in vivo (in an animal model of lymphoma and CRS) the therapeutic potential of therapies aimed at repairing the hematopoietic bone marrow microenvironment, such as the use of allogeneic mesenchymal cells (MSC) from healthy donors and MSC-derived extracellular vesicles (MSC-EV) studying their effects on inflammatory mediators, hematopoiesis and the cytotoxic effect of CAR-T.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Lymphoma B Cell; CAR-T Therapy; Cytopenia; Hematopoietic Niche; Inflammation

Outcome Measures

Primary Outcomes (3)

• Characterizing hematopoietic niche post CAR-T Therapy

  To analyze the characteristics of the hematopoietic niche in patients experiencing prolonged cytopenias post CAR-T cell therapy compared to those without cytopenias and their pre-treatment status.

  36 months

• Characterizing systemic inflammation post CAR-T Therapy

  To analyze the characteristics of systemic inflammatory status in patients experiencing prolonged cytopenias post CAR-T cell therapy compared to those without cytopenias and their pre-treatment status.

  36 months

• Characterizing medullary inflammation post CAR-T Therapy

  To analyze the characteristics of medullary inflammatory status in patients experiencing prolonged cytopenias post CAR-T cell therapy compared to those without cytopenias and their pre-treatment status.

  36 months

Interventions

CAR-T cell therapy BIOLOGICAL

Patients with diffuse large B-cell lymphoma undergoing consecutive commercial CAR-T therapy at the University Hospital of Salamanca

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with diffuse large B-cell lymphoma undergoing consecutive commercial CAR-T therapy at the University Hospital of Salamanca

You may qualify if:

• Patients with diffuse large B-cell lymphoma undergoing consecutive commercial CAR-T therapy
• Over 18 years old
• Sign the informed consent

You may not qualify if:

• Under 18 years old
• Do not sign the informed consent

Sponsors & Collaborators

• Instituto de Investigación Biomédica de Salamanca: lead
• Carlos III Health Institute: collaborator

Study Sites (1)

Complejo Asistencial Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Cytopenia; Inflammation

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Central Study Contacts

Fermín Sánchez-Guijo Martín, PhD MD

CONTACT

+34 923 291384; ferminsg@usal.es

Sandra Muntión Olave, PhD

CONTACT

+34 923 291200; smuntion@usal.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: June 3, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 3, 2024

Record last verified: 2024-05

Locations

ES (1)