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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

I

Instituto de Investigación Biomédica de Salamanca

Status

Enrolling

Conditions

Diffuse Large B Cell Lymphoma

Treatments

Biological: CAR-T cell therapy

Study type

Observational

Funder types

Other

Identifiers

NCT06439173
PI2024 03 1552 (Registry Identifier)
PI23/01107

Details and patient eligibility

About

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.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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

Trial contacts and locations

1

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Central trial contact

Sandra Muntión Olave, PhD; Fermín Sánchez-Guijo Martín, PhD MD

Data sourced from clinicaltrials.gov

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