Clinical trial NCT06439173: 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
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diffuse Large B Cell Lymphoma
Keywords: Lymphoma B Cell
CAR-T Therapy
Cytopenia
Hematopoietic Niche
Inflammation
Lead sponsor: Instituto de Investigación Biomédica de Salamanca
Sponsor class: OTHER
Collaborators: name: Carlos III Health Institute
First posted: 2024-06-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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

Primary outcomes:
measure: Characterizing hematopoietic niche post CAR-T Therapy
timeFrame: 36 months
measure: Characterizing systemic inflammation post CAR-T Therapy
timeFrame: 36 months
measure: Characterizing medullary inflammation post CAR-T Therapy
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
Study officials:
References: