Molecular-genetic Characterization in Patients Undergoing CAR-T Cell Infusion

NCT05807789 | Recruiting

• 1 other identifier: CAR_22
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, the application of increasingly advanced methods of ex-vivo cell culture and cell engineering has made it possible to develop new cellular therapeutic platforms including the "CAR (Chimeric Antigen Receptor) - T cell therapy". CAR-T cell therapy is a therapy that uses T lymphocytes engineered to express a chimeric receptor directed against a specific antigen, theoretically applicable to the treatment of all neoplasms but currently more widely used in the treatment of haematological malignancies. One of the most innovative aspects introduced with CAR-T cell therapy is that of living-drug, cells that act as a drug as well as a means to build specific immunity against the neoplasm. The advantages of this therapy are therefore represented by the possibility of refueling the patient's immunity, deficient in the control of the neoplastic disease, with lymphocytes capable of expressing an antineoplastic activity with mechanisms not subject to restriction of HLA-mediated antigen recognition. However, the use of CAR-T therapies is not free from potentially serious and sometimes lethal adverse events; in the toxicity profile the following are recognizable as peculiar:

• cytokine release syndrome (CRS)
• B-cell aplasia (hypogammaglobulinemia)
• neurological adverse reactions
• haematological toxicity
• infections. Therefore, considering that on the one hand adverse events are not negligible and on the other hand that a percentage \> 50% of patients lose the response obtained, it is necessary to improve the therapeutic profile of CAR-T cell therapy by increasing its efficacy and reducing its toxicity . Both of these strategies are linked to the understanding of the resistance mechanisms of neoplastic cells, as well as to the biology of CAR-T cells and of all the cellular (microenvironment) and non-cellular systems with which they interact.

Conditions

Hematologic Malignancy

Keywords

CAR-T

Outcome Measures

Primary Outcomes (2)

• Genomic studies

  Genomic studies in peripheral blood samples taken from patients affected by hematological malignancies undergoing CAR-T cell therapy, in order to identify correlations between neoplastic cell signatures and response to therapy (evaluated according to laboratory and instrumental standards).

  3 years

• Study of CAR+ and CAR- lymphoid populations and of myeloid populations

  Study of CAR+ and CAR- lymphoid populations and of myeloid populations with single-cell RNA sequencing platforms in peripheral blood samples in order to understand the cellular dynamics related to clinical outcomes such as response to therapy (evaluated according to laboratory and instrumental standards) and adverse events (CRS, ICANS, sHLH, coagulopathy, cytopenias, and autoimmune dyscrasias).

  3 years

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will be proposed to all patients aged ≥ 18 years undergoing CAR-T cell infusion at the Departmental Program of Advanced Cellular Therapies of the IRCCS AOU of Bologna

You may qualify if:

• Patients aged ≥ 18 years.
• Patients with haematological pathology hospitalized for CAR-T cell infusion therapeutic program (with Marketing Authorization) at the Departmental Program of Advanced Cellular Therapies, of the IRCCS AOU of Bologna
• Patients with express consent to participate in this study, acquired by signing the informed consent.

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

Programma Dipartimentale Terapie Cellulari Avanzate

Bologna, Italy, 40138, Italy

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Francesca Bonifazi, MD

CONTACT

+39 0512143799; francesca.bonifazi@unibo.it

Enrica Tomassini, MB

CONTACT

+39 0512143799; enrica.tomassini2@unibo.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Director of Hematopoietic Stem Cell Transplant Program

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 11, 2023
• Study Start: February 23, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)