Italian Observational Study on CAR-T Therapy for Lymphoma
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Diffuse Low Grade B-Cell Lymphoma, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Mantle Cell Lymphoma, Follicular Lymphoma. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
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
Overview
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.
Primary outcome measures
- Feasibility of the CAR-T cells treatment in lymphomas in the italian real life practice [Time frame: 10 years enrollment, minimum 1 year follow-up]
- Efficacy of the CAR-T cells treatment in lymphomas in the italian real life practice [Time frame: 10 years enrollment, minimum 1 year follow-up]
Secondary outcome measures (12)
- Evaluation of Outcome: Overall Response rate (ORR), according to Lugano criteria. [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of Outcome: Overall survival (OS), according to Lugano criteria. [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of Outcome: Progression free survival (PFS) [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of Outcome: duration of response (DoR) [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of Outcome: Overall Response rate (ORR) [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of Outcome: Overall survival (OS) [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of Outcome: non-relapse mortality (NRM) [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of safety (CRS, neurotoxicity, infections, cytopenias, B cell aplasia, second malignancies) with particular attention to the safety in the new indications [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of bridging therapy: safety [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of bridging therapy: efficay [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of salvage therapy after CAR-T failure [Time frame: 10 years, minimum f-up 1 year]
- Evaluation of salvage therapy after CAR-T failure [Time frame: 10 years, minimum f-up 1 year]
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Italy · 1 center
- Fondazione IRCCS Istituto Nazionale Tumori — Milan
Publications
- Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, Link BK, Hay A, Cerhan JR, Zhu L, Boussetta S, Feng L, Maurer MJ, Navale L, Wiezorek J, Go WY, Gisselbrecht C. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 Oct 19;130(16):1800-1808. doi: 10.1182/blood-2017-03-769620. Epub 2017 Aug 3. PMID 28774879
- Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang PMID 29226797
- Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large PMID 30518502
- Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel PMID 36821768
- Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refra PMID 34516954
- Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 1 PMID 32888407
- Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Munoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axica PMID 34891224
- Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Crotta A, Montheard S, Previtali A, Ogasawara K, Kamdar M. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023 Apr 6;141(14):1675-1684. doi: 10.1182 PMID 36542826
Identifiers
NCT: NCT06339255 · INT 180/19