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

May 31, 2024 updated by: Instituto de Investigación Biomédica de Salamanca

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.

Study Overview

Status

Recruiting

Conditions

Diffuse Large B Cell Lymphoma

Intervention / Treatment

Biological: CAR-T cell therapy

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Fermín Sánchez-Guijo Martín, PhD MD
Phone Number: +34 923 291384
Email: ferminsg@usal.es

Study Contact Backup

Name: Sandra Muntión Olave, PhD
Phone Number: 55031 +34 923 291200
Email: smuntion@usal.es

Study Locations

Spain
- - Salamanca, Spain, 37007
    - Recruiting
    - Complejo Asistencial Universitario de Salamanca
    - Contact:
      
      Fermín Sánchez-Guijo Martín, PhD MD
      
      Phone Number: +34 923 291384
      
      Email: ferminsg@usal.es
    - Contact:
      
      Sandra Muntión Olave, PhD
      
      Phone Number: 55015 +34 923 291200
      
      Email: smuntion@usal.es

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

N/A

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterizing hematopoietic niche post CAR-T Therapy Time Frame: 36 months	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 Time Frame: 36 months	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 Time Frame: 36 months	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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto de Investigación Biomédica de Salamanca

Collaborators

Carlos III Health Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2024

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

April 18, 2024

First Submitted That Met QC Criteria

May 31, 2024

First Posted (Actual)

June 3, 2024

Study Record Updates

Last Update Posted (Actual)