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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06439173
• Other study ID #: PI23/01107
• Secondary ID: PI2024 03 1552
• Status: Recruiting
• Start date: January 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Instituto de Investigación Biomédica de Salamanca
• Contact: Fermín Sánchez-Guijo Martín, PhD MD
• Phone: +34 923 291384
• Email: ferminsg[@]usal.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2026
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Spain	Complejo Asistencial Universitario de Salamanca	Salamanca

Sponsors (2)

Lead Sponsor	Collaborator
Instituto de Investigación Biomédica de Salamanca	Carlos III Health Institute

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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