Clinical trial NCT06339255: Italian Observational Study on CAR-T Therapy for Lymphoma
Official title: A Multicenter Prospective Observational Study on Chimeric Antigen Receptor (CAR) T-cell Therapy for Lymphoma: Monitoring Feasibility, Efficacy, Toxicity and Biomarkers in a Real Life Setting
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Diffuse Low Grade B-Cell Lymphoma
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
Mantle Cell Lymphoma
Follicular Lymphoma
Keywords: CAR-T
Lymphoma
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
Collaborators: name: Annalisa Chiappella
name: Cristiana Carniti
name: Anna Dodero
First posted: 2024-04-01
Enrollment: 5300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with diagnosis of DLCBL, PMBCL, MCL and FL eligible for CAR-T treatment with commercialy available products in Italy.

Brief summary: The goal of this observational study on chimeric antigen receptor T-cell therapy is to monitor the feasibility, efficacy, toxicity and biomarkers in a real life setting.

Partecipants will be asked to agree to their clinical data collection and to partecipate to the optional biological study that aims to evaluate biomarkers of toxicity and response (clinical characteristics, cytokine profile, cellcomposition and type of the CAR-T cell product, lymphoma genomics). The study will evaluate even the disease response according to lugano criteria by PET and CT in routine clinical activity.

Detailed description: This observational prosopective multicenter study aims to:

1. evaluate the feasibility of CAR T-cell treatment in the real-life setting, with particular regard to eligible patients versus those subjected to leukapheresis versus those finally treated.
2. evaluate the survival outcome of PMBCL, DLBCL, MCL and FL patients treated with CAR T-cells versus those potentially eligible, but excluded from cellular therapy for other causes (either related to the patient or to the manufacturing);
3. monitor the incidence of early and late AEs up to three year after CAR-T;
4. evaluate disease response and immune recovery biomarkers at different time-points up after CAR-T (when clinically indicated or using blood sampling leftover);
5. evaluate biomarkers of toxicity and response (clinical characteristics, cytokine profile, cell composition and type of the CAR T-cell product, lymphoma genomics).
6. evaluate disease response according to Lugano criteria by PET and CT in routine clinical activity.

Primary Objective:

• Feasibility and efficacy of the treatment in the real life practice

Secondary Objectives:

* Evaluation of Outcome \[Response rate (ORR), Overall survival (OS), Progression free survival (PFS), duration of response (DoR) non-relapse mortality (NRM)\] according to Lugano criteria.
* Evaluation of safety (CRS, neurotoxicity, infections, cytopenias, B cell aplasia, second malignancies) with particular attention to the safety in the new indications
* Evaluation of bridging therapy (outcome and safety)
* Evaluation of salvage therapy after CAR-T failure (outcome and safety)
* Comparison of the different CAR T-cell products (time from patient screening to infusion, disease response and safety)
* Comparison of the different histotypes (PMBCL, DLBCL, MCL FL) according to CAR-T cell products

Biological Studies

* Characterization of biomarkers of early response (circulating tumor cell free DNA versus PET and CT scans)
* Characterization of toxicity biomarkers
* Analysis of the immune reconstitution and CAR-T expression Radiomics Evaluation
* Influence of PET quantitative parameters (tMTV, Distance max, Distance max bulky, metabolic changes between baseline and +30 and +90 after CAR T-cell infusion (ΔSUV max) on outcome
* Influence of PET quantitative parameters (tMTV, Distance max, Distance max bulky, metabolic changes between baseline and +30 and +90 after CAR T-cell infusion (ΔSUV max) on outcome.

Primary endpoint:

to evaluate the percentage of patients infused versus those eligible and leukoapheresed to evaluate the overall response and survival at one year of the patients treated with CAR T cells.

Secondary endpoints:

Overall response rate (ORR) at 3-6-12-18 months Overall survival (OS) for all patients included in the study OS, Progression free survival (PFS), Event free survival (EFS), and duration of response (DoR), non-relapse mortality (NRM) after CAR T-cell therapy at one,two years and 5 years Incidence and grading of CRS and neurotoxicity Number of patients receiving a bridging therapy before lymphodepletion Intensive Care Unit admission rate for all treated patients Lymphoma genomics and circulating cell free DNA as early response biomarker Characterization of toxicity biomarkers Analysis of immune reconstitution and CAR-T expression Early Adverse event (grading/onset/severity/treatment) Long term Safety (AE grading/onset/severity/treatment) Incidence of second malignancies Evaluation of quantitative parameters of PET by central review, when applicable in selected sites This is an observational multicenter prospective study enrolling all consecutive patients referred to the Italian hematologic centers already qualified for CAR T-cell treatment with relapsed/refractory DLBCL, PMBCL, MCL and FL. The screening will be done according to the axi-cel, tisagen-cel, brexucabtagene autoleucel and lisocabtagene maraleucel label criteria, the eligibility of a given patient to CAR-T will be definedaccording to AIFA criteria.

All patients eligible to CAR-T will be consecutively enrolled Biological samples will be stored at each institution or centralized at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milano. Fondazione Italiana Linfomi (FIL) will be in charge of the GCP management of the study. Web-based CRF are prepared by FIL.

Eligibility criteria: Inclusion Criteria:

* Patients with diagnosis of DLCBL, PMBCL, MCL and FL eligible for CAR-T treatment with commercialy available products in Italy.

Exclusion Criteria:

* Not applicable

Primary outcomes:
measure: Feasibility of the CAR-T cells treatment in lymphomas in the italian real life practice
timeFrame: 10 years enrollment, minimum 1 year follow-up
measure: Efficacy of the CAR-T cells treatment in lymphomas in the italian real life practice
timeFrame: 10 years enrollment, minimum 1 year follow-up
Secondary outcomes:
measure: Evaluation of Outcome: Overall Response rate (ORR), according to Lugano criteria.
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of Outcome: Overall survival (OS), according to Lugano criteria.
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of Outcome: Progression free survival (PFS)
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of Outcome: duration of response (DoR)
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of Outcome: Overall Response rate (ORR)
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of Outcome: Overall survival (OS)
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of Outcome: non-relapse mortality (NRM)
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of safety (CRS, neurotoxicity, infections, cytopenias, B cell aplasia, second malignancies) with particular attention to the safety in the new indications
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of bridging therapy: safety
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of bridging therapy: efficay
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of salvage therapy after CAR-T failure
timeFrame: 10 years, minimum f-up 1 year
measure: Evaluation of salvage therapy after CAR-T failure
timeFrame: 10 years, minimum f-up 1 year
measure: Comparison of the different CAR T-cell products (time from patient screening to infusion, disease response and safety)
timeFrame: 10 years, minimum f-up 1 year
measure: Comparison of the different histotypes (PMBCL, DLBCL, MCL FL) according to CAR-T cell products
timeFrame: 10 years, minimum f-up 1 year
Other outcomes:
measure: Characterization of biomarkers of early response (circulating tumor cell free DNA versus PET and CT scans)
timeFrame: 10 years, minimum f-up 1 year
measure: Characterization of toxicity biomarkers
timeFrame: 10 years, minimum f-up 1 year
measure: Analysis of the immune reconstitution
timeFrame: 10 years, minimum f-up 1 year
measure: Analysis of the CAR-T expression
timeFrame: 10 years, minimum f-up 1 year
measure: Influence of PET quantitative parameters: tMTV changes between baseline and +30 and +90 after CAR T-cell infusion (ΔSUV max) related to outcome
timeFrame: 10 years, minimum f-up 1 year
measure: Influence of PET quantitative parameters: Distance max
timeFrame: 10 years, minimum f-up 1 year
measure: Influence of PET quantitative parameters: Distance max bulky
timeFrame: 10 years, minimum f-up 1 year
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
Study officials:
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