CAR-T Therapy: Safety, Efficacy, and Immune-Escape Mechanisms (OSR-CAR-T)

Biological Observational Study for Monitoring Patients Receiving Chimeric Antigen Receptor T-cell (CAR-T) Therapies, Identifying Predictive Factors of Efficacy and Safety, and Understanding Immune-escape Mechanisms to Optimize Existing Platforms

The study is a biological, drug-related, non-interventional observational study with both retrospective and prospective components.

No experimental diagnostic procedures, investigational medicinal products, or medical devices will be used, and samples will be collected as part of routine clinical practice.

Study Overview

• Status: Recruiting
• Conditions: CAR-T Cell Therapy; Bispecific Antibodies

Detailed Description

This is a retrospective and prospective, non-interventional, biological observational study involving adult patients who receive or have received Chimeric Antigen Receptor T-cell (CAR-T) therapy or bispecific antibody therapy at IRCCS Ospedale San Raffaele.

The primary objective is to characterize patients undergoing these treatments to identify biomarkers predictive of treatment response and toxicity, support therapeutic decision-making, and identify novel therapeutic targets. The study will investigate tumor cell and tumor microenvironment signatures, biomarkers of CAR-T product fitness, and clinical variables potentially associated with treatment outcomes. These variables will include prior lines of treatment, T-cell composition before manipulation, the composition and activation status of host T-cell and myeloid cell populations, timing of cell collection, and bridging therapy.

The study will also monitor the kinetics and phenotypic and functional characteristics of CAR-T cells following infusion to investigate their association with treatment efficacy and safety. Furthermore, the study aims to improve understanding of the biological mechanisms underlying treatment resistance and immune escape, with the ultimate goal of optimizing existing therapeutic platforms.

The primary endpoints are overall response rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) following treatment ; the incidence of cytokine release syndrome (CRS); the incidence of neurotoxicity; and progression-free survival (PFS), defined as the time from the applicable treatment initiation or infusion to disease progression or death, according to the study-specific assessment criteria.

These endpoints will be evaluated in relation to biological signatures, CAR-T product characteristics, clinical variables, and post-infusion CAR-T cell kinetics and functionality.

Secondary objectives include the establishment, implementation, and maintenance of an integrated database combining clinical information with data obtained through laboratory monitoring. The study will also assess the applicability of biomarkers previously identified as predictive of response and/or toxicity in CAR-T-treated patients to patients receiving bispecific antibody therapy.

Biological samples will be collected as part of routine clinical practice or retrieved from existing biological sample collections, where available. No experimental diagnostic procedures, investigational medicinal products, or investigational medical devices will be introduced as part of the study.

Eligibility criteria

• Eligible participants must be adults aged 18 years or older and meet at least one of the following criteria:
• Candidates for CAR-T-cell therapy who have signed at least an initial informed consent for evaluation for this treatment at the study center.
• Patients who have previously provided informed consent for participation in the Hematological Malignancies Biobank (Biobanca Neoplasie Ematologiche) and for whom stored biological samples are available.
• Candidates for bispecific antibody therapy who have signed at least an initial informed consent for evaluation for this treatment at the study center.

Exclusion Criteria

- Patients participating in clinical protocols that explicitly prohibit participation in biological observational studies will be excluded.

• Study Type: Observational
• Enrollment (Estimated): 225

Contacts and Locations

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20132
      • Recruiting
      • IRCCS San Raffaele Hospital
      • Contact: Fabio Ciceri; Phone Number: +39 02-2643-9396; Email: ciceri.clinicaltrials@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients aged 18 years or older evaluated for CAR-T-cell therapy or bispecific antibody therapy at IRCCS Ospedale San Raffaele, as well as patients with available biological samples stored in the Hematological Malignancies Biobank who have provided informed consent. Patients participating in clinical trial protocols that explicitly prohibit participation in biological observational studies will be excluded.

Description

Inclusion Criteria:

To achieve the objectives of this study, biological samples will be obtained from patients aged 18 years or older who meet at least one of the following inclusion criteria:

• Patients eligible for CAR-T-cell therapy who have signed at least an initial informed consent for evaluation for this treatment at our center.
• Patients who have previously signed the informed consent for the Hematological Malignancies Biobank (Biobanca Neoplasie Ematologiche) and for whom stored biological samples are available.
• Patients eligible for bispecific antibody therapy who have signed at least an initial informed consent for evaluation for this treatment at our center.

Exclusion Criteria:

• Participation in clinical trial protocols that explicitly prohibit participation in biological observational studies.

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: OTHER

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients treated with CAR-T
Patients treated with bispecific antibodies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Proportion of patients achieving a complete response (CR) or partial response (PR) following treatment.	Up to 6 months after treatment
Incidence of Cytokine Release Syndrome (CRS)	Incidence of CRS and distribution of CRS severity grades following treatment, according to the applicable grading criteria.	1 month after treatment
Incidence of Neurotoxicity	Incidence of ICANS and distribution of ICANS severity grades following treatment, according to the applicable grading criteria.	1 month after treatment
Progression-Free Survival (PFS)	Time from treatment initiation to disease progression or death from any cause.	12 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development and Maintenance of an Integrated Clinical and Laboratory Database	Establishment, implementation, and maintenance of an integrated database combining clinical information with data obtained from laboratory monitoring.	Through study completion, an average of 9 years
Evaluation of CAR-T-Associated Biomarkers in Patients Receiving Bispecific Antibody Therapy	Assessment of the relevance of biomarkers identified as predictors of treatment response and/or toxicity in CAR-T-treated patients in patients receiving bispecific antibodies directed against the same therapeutic targets.	Up to 4 years after the treatment

Collaborators and Investigators

• Sponsor: Ciceri Fabio

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2023
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: October 19, 2026
• First Submitted That Met QC Criteria: October 28, 2026
• First Posted (Actual): November 4, 2026

Study Record Updates

• Last Update Posted (Actual): November 4, 2026
• Last Update Submitted That Met QC Criteria: October 28, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: OSR-CAR-T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No