Italian Observational Study on CAR-T Therapy for Lymphoma (CART-SIE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Primary Mediastinal Large B-cell Lymphoma (PMBCL); Diffuse Low Grade B-Cell Lymphoma

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.

• Study Type: Observational
• Enrollment (Estimated): 5300

Contacts and Locations

• Study Contact: Name: Paolo Corradini, Professor; Phone Number: +39 02 2390 2950; Email: paolo.corradini@istitutotumori.mi.it
• Study Contact Backup: Name: Anisa Bermema, PhD; Phone Number: +39 02 2390 3146; Email: anisa.bermema@istitutotumori.mi.it

Study Locations

• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale Tumori
    • Contact: Paolo Corradini, Professor; Phone Number: +39 02 2390 2950; Email: paolo.corradini@istitutotumori.mi.it
    • Contact: Anisa Bermema, PhD; Phone Number: +39 02 2390 3145; Email: anisa.bermema@istitutotumori.mi.it
    • Sub-Investigator: Annalisa Chiappella, MD
    • Sub-Investigator: Anna Dodero, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of the CAR-T cells treatment in lymphomas in the italian real life practice	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. The percentage of patients infused will be estimated as the number of patients infused divided by the total number of those declared eligible; the corresponding exact confidence intervals at 95% will also be estimated.	10 years enrollment, minimum 1 year follow-up
Efficacy of the CAR-T cells treatment in lymphomas in the italian real life practice	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)	10 years enrollment, minimum 1 year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Outcome: Overall Response rate (ORR), according to Lugano criteria.	Overall response rate (ORR): the percentage of responding patients will be estimated as the number of patients with complete response (CR) + partial response (PR) divided by the total number of patients assessable at each specific timepoint (3-6-12-18 months). Patients not assessable for response for any reason will be considered as non-responding in the calculation of the response rate. The exact 95% confidence intervals of the response percentage will also be estimated.	10 years, minimum f-up 1 year
Evaluation of Outcome: Overall survival (OS), according to Lugano criteria.	Overall survival (OS): time will be measured as the interval between the date of CAR-T infusion and the date of death for all causes, with censoring at the date of the latest follow-up in alive patients. OS curves will be estimated with the Kaplan Meier method.	10 years, minimum f-up 1 year
Evaluation of Outcome: Progression free survival (PFS)	Progression-free survival (PFS): time will be measured as the interval between the CAR-T infusion and the date of progression disease (PD), or death, whichever occurs first.	10 years, minimum f-up 1 year
Evaluation of Outcome: duration of response (DoR)	Duration of Response (DoR): for patients who will respond to treatment, the duration of response will be measured as the interval between the response achievement and the date of progression or death, whichever occurs first, with censoring at the date of the latest follow-up in alive patients without progression. DoR curves will be estimated with the Kaplan Meier method.	10 years, minimum f-up 1 year
Evaluation of Outcome: Overall Response rate (ORR)	Overall response rate (ORR): the percentage of responding patients will be estimated as the number of patients with complete response (CR) + partial response (PR) divided by the total number of patients assessable at each specific timepoint (3-6-12-18 months). Patients not assessable for response for any reason will be considered as non-responding in the calculation of the response rate. The exact 95% confidence intervals of the response percentage will also be estimated.	10 years, minimum f-up 1 year
Evaluation of Outcome: Overall survival (OS)	Overall survival (OS): time will be measured as the interval between the date of CAR-T infusion and the date of death for all causes, with censoring at the date of the latest follow-up in alive patients. OS curves will be estimated with the Kaplan Meier method.	10 years, minimum f-up 1 year
Evaluation of Outcome: non-relapse mortality (NRM)	Non-relapse mortality (NRM) after CAR-T cell therapy: time will be measured as the interval between the date of treatment start and the date of non-relapse death, with censoring at the date of the latest follow-up in alive patients without relapse. NRM cumulative incidence curves will be estimated regarding disease recurrence as competing event, and between groups comparisons will be performed using the Gray test.	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	CRS and ICANS will be measured according to ASCTC. Other toxicities will be measured according to CTCAE.	10 years, minimum f-up 1 year
Evaluation of bridging therapy: safety	Bridging therapy will be analysed in terms of safety as per adverse event occurrence (according to CTCAE).	10 years, minimum f-up 1 year
Evaluation of bridging therapy: efficay	Bridging therapy will be analysed in terms of efficacy in terms of response achievement compared to response assessment prior to bridging therapy.	10 years, minimum f-up 1 year
Evaluation of salvage therapy after CAR-T failure	In case of relapse after CAR-T, data regarding salvage therapy will be collected in terms of reponse (PFS)	10 years, minimum f-up 1 year
Evaluation of salvage therapy after CAR-T failure	In case of relapse after CAR-T, data regarding salvage therapy will be collected in terms of survival (OS).	10 years, minimum f-up 1 year
Comparison of the different CAR T-cell products (time from patient screening to infusion, disease response and safety)	Time form screening to infusion will be compared between CAR-T products, disease response will be evaluated in terms of CR, PR and SD.	10 years, minimum f-up 1 year
Comparison of the different histotypes (PMBCL, DLBCL, MCL FL) according to CAR-T cell products	Study popoulation will be analysed in terms of reponse and type CAR-T product.	10 years, minimum f-up 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of biomarkers of early response (circulating tumor cell free DNA versus PET and CT scans)	To study the circulating cell free DNA modulation during time, besides descriptive statistical analyses, we will use non parametric factorial models for longitudinal data [Brunner E, Domhof S, Langer F. Nonparametric analysis of longitudinal data in factorial experiments. John Wiley & Sons 2002, New York]. Such models were chosen because they allow take into account measurement incompleteness and positive asymmetry of biomarker distribution, and because they are robust to outliers. The models also allow to test the difference in the longitudinal profiles according to specific covariates.	10 years, minimum f-up 1 year
Characterization of toxicity biomarkers	Biomarkers will be analysed in relation to toxicities occurrence on order to identify predictors of toxicity onset and severity	10 years, minimum f-up 1 year
Analysis of the immune reconstitution	Evaluate disease response and immune recovery biomarkers at different time-points up after CAR-T (when clinically indicated or using blood sampling leftover)	10 years, minimum f-up 1 year
Analysis of the CAR-T expression	Evaluate the persistence of CAR-T after administration	10 years, minimum f-up 1 year
Influence of PET quantitative parameters: tMTV changes between baseline and +30 and +90 after CAR T-cell infusion (ΔSUV max) related to outcome	In our study, the PET scans will be collected and anonymized. A central review with analyses of quantitative parameters will be performed. Evaluation of baseline tMTV calculated by MTV4 method which automatically segments area with SUV ≥4.0.	10 years, minimum f-up 1 year
Influence of PET quantitative parameters: Distance max	In our study, the PET scans will be collected and anonymized. A central review with analyses of quantitative parameters will be performed. Dmax between baseline and +30 and +90 after CAR-T cells infusion	10 years, minimum f-up 1 year
Influence of PET quantitative parameters: Distance max bulky	In our study, the PET scans will be collected and anonymized. A central review with analyses of quantitative parameters will be performed. Dmax bulk is the maximum distance to the bulk and we wil analyse its change between baseline and day +30 and +90.	10 years, minimum f-up 1 year

Collaborators and Investigators

• Sponsor: Paolo Corradini
• Collaborators: Annalisa Chiappella; Cristiana Carniti; Anna Dodero

Publications and helpful links

General Publications

• Kochenderfer JN, Somerville RPT, Lu T, Shi V, Bot A, Rossi J, Xue A, Goff SL, Yang JC, Sherry RM, Klebanoff CA, Kammula US, Sherman M, Perez A, Yuan CM, Feldman T, Friedberg JW, Roschewski MJ, Feldman SA, McIntyre L, Toomey MA, Rosenberg SA. Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels. J Clin Oncol. 2017 Jun 1;35(16):1803-1813. doi: 10.1200/JCO.2016.71.3024. Epub 2017 Mar 14.
• Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Milpied N, Fung H, Topp MS, Houot R, Beitinjaneh A, Peng W, Zheng L, Rossi JM, Jain RK, Rao AV, Reagan PM. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020 Apr 2;382(14):1331-1342. doi: 10.1056/NEJMoa1914347.
• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
• 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. Erratum In: Blood. 2018 Feb 1;131(5):587-588.
• 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 D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10.
• 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 B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. doi: 10.1016/S1470-2045(18)30864-7. Epub 2018 Dec 2.
• 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 in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. doi: 10.1182/blood.2022018893.
• 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 refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. doi: 10.1016/S1470-2045(21)00375-2. Epub 2021 Sep 10.
• 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 19;396(10254):839-852. doi: 10.1016/S0140-6736(20)31366-0. Epub 2020 Sep 1.
• 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. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. doi: 10.1056/NEJMoa2116133. Epub 2021 Dec 11.
• 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/blood.2022018730.
• Monfrini C, Stella F, Aragona V, Magni M, Ljevar S, Vella C, Fardella E, Chiappella A, Nanetti F, Pennisi M, Dodero A, Guidetti A, Corradini P, Carniti C. Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects In Vivo Expansion and Disease Response in Patients with Large B-cell Lymphoma. Clin Cancer Res. 2022 Aug 2;28(15):3378-3386. doi: 10.1158/1078-0432.CCR-22-0164.
• Biancon G, Gimondi S, Vendramin A, Carniti C, Corradini P. Noninvasive Molecular Monitoring in Multiple Myeloma Patients Using Cell-Free Tumor DNA: A Pilot Study. J Mol Diagn. 2018 Nov;20(6):859-870. doi: 10.1016/j.jmoldx.2018.07.006. Epub 2018 Aug 28.
• Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, Lawrence MS, Roemer MGM, Li AJ, Ziepert M, Staiger AM, Wala JA, Ducar MD, Leshchiner I, Rheinbay E, Taylor-Weiner A, Coughlin CA, Hess JM, Pedamallu CS, Livitz D, Rosebrock D, Rosenberg M, Tracy AA, Horn H, van Hummelen P, Feldman AL, Link BK, Novak AJ, Cerhan JR, Habermann TM, Siebert R, Rosenwald A, Thorner AR, Meyerson ML, Golub TR, Beroukhim R, Wulf GG, Ott G, Rodig SJ, Monti S, Neuberg DS, Loeffler M, Pfreundschuh M, Trumper L, Getz G, Shipp MA. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018 May;24(5):679-690. doi: 10.1038/s41591-018-0016-8. Epub 2018 Apr 30. Erratum In: Nat Med. 2018 Aug;24(8):1292. Nat Med. 2018 Aug;24(8):1290-1291.
• Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M, De Moerloose B, Nemecek ER, Bittencourt H, Hiramatsu H, Buechner J, Davies SM, Verneris MR, Nguyen K, Brogdon JL, Bitter H, Morrissey M, Pierog P, Pantano S, Engelman JA, Winckler W. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med. 2018 Oct;24(10):1504-1506. doi: 10.1038/s41591-018-0146-z. Epub 2018 Oct 1.
• Singh N, Perazzelli J, Grupp SA, Barrett DM. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Sci Transl Med. 2016 Jan 6;8(320):320ra3. doi: 10.1126/scitranslmed.aad5222.
• Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Gooley T, Li D, Cherian S, Chen X, Pender BS, Hawkins RM, Vakil A, Steinmetz RN, Acharya UH, Cassaday RD, Chapuis AG, Dhawale TM, Hendrie PC, Kiem HP, Lynch RC, Ramos J, Shadman M, Till BG, Riddell SR, Maloney DG, Turtle CJ. The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells. Blood. 2019 Apr 25;133(17):1876-1887. doi: 10.1182/blood-2018-11-887067. Epub 2019 Feb 19.
• Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015 Aug;15(8):486-99. doi: 10.1038/nri3862.
• Oliveira G, Ruggiero E, Stanghellini MT, Cieri N, D'Agostino M, Fronza R, Lulay C, Dionisio F, Mastaglio S, Greco R, Peccatori J, Aiuti A, Ambrosi A, Biasco L, Bondanza A, Lambiase A, Traversari C, Vago L, von Kalle C, Schmidt M, Bordignon C, Ciceri F, Bonini C. Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory. Sci Transl Med. 2015 Dec 9;7(317):317ra198. doi: 10.1126/scitranslmed.aac8265. Erratum In: Sci Transl Med. 2015 Dec 23;7(319):319er9. D'Agostino, Mattio [corrected to D'Agostino, Mattia].
• Vercellino L, Di Blasi R, Kanoun S, Tessoulin B, Rossi C, D'Aveni-Piney M, Oberic L, Bodet-Milin C, Bories P, Olivier P, Lafon I, Berriolo-Riedinger A, Galli E, Bernard S, Rubio MT, Bossard C, Meignin V, Merlet P, Feugier P, Le Gouill S, Ysebaert L, Casasnovas O, Meignan M, Chevret S, Thieblemont C. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020 Nov 24;4(22):5607-5615. doi: 10.1182/bloodadvances.2020003001.
• Dean EA, Mhaskar RS, Lu H, Mousa MS, Krivenko GS, Lazaryan A, Bachmeier CA, Chavez JC, Nishihori T, Davila ML, Khimani F, Liu HD, Pinilla-Ibarz J, Shah BD, Jain MD, Balagurunathan Y, Locke FL. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020 Jul 28;4(14):3268-3276. doi: 10.1182/bloodadvances.2020001900.
• Casasnovas RO, Ysebaert L, Thieblemont C, Bachy E, Feugier P, Delmer A, Tricot S, Gabarre J, Andre M, Fruchart C, Mounier N, Delarue R, Meignan M, Berriolo-Riedinger A, Bardet S, Emile JF, Jais JP, Haioun C, Tilly H, Morschhauser F. FDG-PET-driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study. Blood. 2017 Sep 14;130(11):1315-1326. doi: 10.1182/blood-2017-02-766691. Epub 2017 Jul 12.
• Cottereau AS, Nioche C, Dirand AS, Clerc J, Morschhauser F, Casasnovas O, Meignan M, Buvat I. 18F-FDG PET Dissemination Features in Diffuse Large B-Cell Lymphoma Are Predictive of Outcome. J Nucl Med. 2020 Jan;61(1):40-45. doi: 10.2967/jnumed.119.229450. Epub 2019 Jun 14.
• Guidetti A, Dodero A, Lorenzoni A, Pizzamiglio S, Argiroffi G, Chiappella A, Bagnoli F, Marasco V, Carniti C, Monfrini C, Seregni E, Pennisi M, Verderio P, Alessi A, Corradini P. Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. Cancer. 2023 Jan 15;129(2):255-263. doi: 10.1002/cncr.34532. Epub 2022 Nov 17.
• Dodero A, Bramanti S, Di Trani M, Pennisi M, Ljevar S, Chiappella A, Massimo M, Guidetti A, Corrado F, Nierychlewska PM, Di Rocco A, Lorenzini D, Daoud R, De Philippis C, Santoro A, Carlo-Stella C, Corradini P. Outcome after chimeric antigen receptor (CAR) T-cell therapy failure in large B-cell lymphomas. Br J Haematol. 2024 Jan;204(1):151-159. doi: 10.1111/bjh.19057. Epub 2023 Sep 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2019
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: March 24, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Mantle-Cell
• Other Study ID Numbers: INT 180/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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