ZUMA-1

Podcasts, YouTube videos and X posts in our index that name this trial. A report screens them, searches for more and cites what clinicians said when it is built.

Official title

A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma

Phase

Phase 1/Phase 2

Status

Completed

Conditions

Refractory Diffuse Large B Cell Lymphoma (DLBCL); Relapsed Diffuse Large B-Cell Lymphoma; Transformed Follicular Lymphoma (TFL); Primary Mediastinal B-cell Lymphoma (PMBCL); High Grade B-cell Lymphoma (HGBCL)

Interventions

Axicabtagene Ciloleucel; Fludarabine; Cyclophosphamide; Levetiracetam; Tocilizumab; Dexamethasone; High-dose methylprednisolone; Bendamustine; Rituximab; Doxorubicin; Prednisone; Vincristine; Ifosfamide; Carboplatin; Etoposide; Gemcitabine; Oxaliplatin; Cisplatin; Methylprednisolone

Arms

• Phase 1 Study: Axicabtagene Ciloleucel and Conditioning Chemotherapy · Experimental
• Phase 2 (Pivotal Study): Cohort 1 · Experimental
• Phase 2 (Pivotal Study): Cohort 2 · Experimental
• Phase 2 (Safety Management Study): Cohort 3 · Experimental
• Phase 2 (Safety Management Study): Cohort 4 · Experimental
• Phase 2 (Safety Management Study): Cohort 5 · Experimental
• Phase 2 (Safety Management Study): Cohort 6 · Experimental

Enrollment

307

Primary outcomes

• Phase 1 Study: Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs)
• Phase 2 Pivotal Study (Cohorts 1 and 2): Overall Response Rate (ORR) as Assessed by Investigator Per Revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
• Phase 2 Safety Management Study (Cohort 3): Percentage of Participants With Treatment-Emergent Cytokine Release Syndrome (CRS) and Neurologic Toxicities by Severity Grades
• Phase 2 Safety Management Study (Cohort 4): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades
• Phase 2 Safety Management Study (Cohort 5): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades
• Phase 2 Safety Management Study (Cohort 6): Percentage of Participants With Treatment-Emergent CRS and Neurologic Toxicities by Severity Grades

Sponsor

Kite, A Gilead Company

Start

Apr 21, 2015

Primary completion

Jul 27, 2023

Results posted

Yes

Registry record

NCT02348216 · updated Jun 4, 2024

• Topp MS, van Meerten T, Wermke M et al. Preliminary Results of Earlier Steroid Use with Axicabtagene Ciloleucel in Patients With Relapsed/Refractory Large B Cell Lymphoma. Poster presented at the American Society of Presented at: American Society of Clinical Oncology Annual Meeting. May 31-June 4, 2019; Chicago, Illinois; Abstract 7558.
• Topp, M, van Meerten T, Houot R, et al. (2019). Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting Abstracts) 134(Suppl 1): 243. Abstract 626.
• Abstract: Oluwole OO, et al. Prophylactic corticosteroid use with axicabtagene ciloleucel in patients with relapsed/refractory large B-cell lymphoma. Transplantation and Cellular Therapy 2021.
• Oluwole OO, Bouabdallah K, Munoz J, De Guibert S, Vose JM, Bartlett NL, Lin Y, Deol A, McSweeney PA, Goy AH, Kersten MJ, Jacobson CA, Farooq U, Minnema MC, Thieblemont C, Timmerman JM, Stiff P, Avivi I, Tzachanis D, Kim JJ, Bashir Z, McLeroy J, Zheng Y, Rossi JM, Johnson L, Goyal L, van Meerten T. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021 Aug;194(4):690-700. doi: 10.1111/bjh.17527. Epub 2021 Jul 22. PubMed 34296427
• Santa Monica, Calif. New Four-Year Data Show Long-Term Survival in Patients With Large B-Cell Lymphoma Treated With Yescarta® in ZUMA-1 Trial. Data presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. December 5, 2020; Abstract 1187
• Max S. Topp, Tom van Meerten, Martin Wermke, Pieternella J. Lugtenburg, Monique C. Minnema, Kevin W. Song, Catherine Thieblemont, Yizhou Jiang, Vicki Plaks, Anne Kerber, Marie José Kersten. Preliminary Results of Earlier Steroid Use With Axicabtagene Ciloleucel in Patients With Relapsed/ Refractory Large B Cell Lymphoma. Poster presented at ASCO 2019 Annual Meeting. June 3, 2019; Abstract 7558
• Sattva S. Neelapu, Caron A. Jacobson, Olalekan O. Oluwole, Javier Munoz, Abhinav Deol, David B. Miklos, Nancy L. Bartlett, Ira Braunschweig, Yizhou Jiang, Jenny J. Kim, Lianqing Zheng, John M. Rossi, Frederick L. Locke. Axicabtagene Ciloleucel (Axi-Cel) In Refractory Large B Cell Lymphoma: Outcomes in Patients ≥ or < 65 Years of Age in the Pivotal Phase 1/2 ZUMA-1 Study. Poster presented at EHA 2019. June 15, 2019; Abstract 1066
• Max S. Topp, Tom van Meerten, Martin Wermke, Pieternella J. Lugtenburg, Monique C. Minnema, Kevin W. Song, Catherine Thieblemont, Yizhou Jiang, Vicki Plaks, Anne Kerber, Marie José Kersten. Axicabtagene Ciloleucel (Axi-Cel) in Patients With Relapsed/Refractory Large B Cell Lymphoma: Preliminary Results of Earlier Steroid Use. Poster presented at EHA 2019. June 15, 2019; Abstract 1067
• Sattva S. Neelapu, John M. Rossi, Caron A. Jacobson, Frederick L. Locke, David B. Miklos, Patrick M. Reagan, Scott Rodig, Lazaros J. Lekakis, Ian W. Flinn, Lianqing Zheng, Francesca Milletti, Edmund Chang, Allen Xue, Vicki Plaks, Jenny J. Kim, Adrian Bot. CD19-Loss With Preservation of Other B Cell Lineage Features in Patients With Large B Cell Lymphoma Who Relapsed Post-Axi-Cel. Blood (ASH Annual Meeting Abstracts) 134(Suppl 1): 203. Abstract 704.
• Sattva S. Neelapu, Frederick L. Locke, Nancy L. Bartlett, Lazaros J. Lekakis, Patrick Reagan, David B. Miklos, Caron A. Jacobson, Ira Braunschweig, Olalekan Oluwole, Tanya Siddiqi, Yi Lin, Michael Crump, John Kuruvilla, Eric Van Den Neste, Umar Farooq, Lynn Navale, Venita DePuy, Jenny J. Kim, Christian Gisselbrecht. A Comparison of Two-Year Outcomes in ZUMA-1 (Axicabtagene Ciloleucel) and SCHOLAR-1 in Patients With Refractory Large B Cell Lymphoma. Blood (ASH Annual Meeting Abstracts) 134(Suppl 1): 4095. Abstract 626.
• Chartier M, Filosto S, Peyret T, Chiney M, Milletti F, Budka J, Ndi A, Dong J, Vardhanabhuti S, Mao D, Duffull S, Dodds M, Shen R. Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma. Clin Pharmacokinet. 2024 Sep;63(9):1283-1299. doi: 10.1007/s40262-024-01413-z. Epub 2024 Sep 6. PubMed 39240498
• Locke FL, Siddiqi T, Jacobson CA, Ghobadi A, Ahmed S, Miklos DB, Perales MA, Munoz J, Fingrut WB, Pennisi M, Gauthier J, Shadman M, Gowda L, Mirza AS, Abid MB, Hong S, Majhail NS, Kharfan-Dabaja MA, Khurana A, Badar T, Lin Y, Bennani NN, Herr MM, Hu ZH, Wang HL, Baer A, Baro E, Miao H, Spooner C, Xu H, Pasquini MC. Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity. Blood. 2024 Jun 27;143(26):2722-2734. doi: 10.1182/blood.2023023447. PubMed 38635762
• 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. PubMed 36821768
• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2. PubMed 34515338
• Maloney DG, Kuruvilla J, Liu FF, Kostic A, Kim Y, Bonner A, Zhang Y, Fox CP, Cartron G. Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. J Hematol Oncol. 2021 Sep 8;14(1):140. doi: 10.1186/s13045-021-01144-9. PubMed 34493319
• Westin JR, Kersten MJ, Salles G, Abramson JS, Schuster SJ, Locke FL, Andreadis C. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021 Oct 1;96(10):1295-1312. doi: 10.1002/ajh.26301. Epub 2021 Aug 13. PubMed 34310745
• Upadhyay R, Boiarsky JA, Pantsulaia G, Svensson-Arvelund J, Lin MJ, Wroblewska A, Bhalla S, Scholler N, Bot A, Rossi JM, Sadek N, Parekh S, Lagana A, Baccarini A, Merad M, Brown BD, Brody JD. A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-cell Immunotherapy. Cancer Discov. 2021 Mar;11(3):599-613. doi: 10.1158/2159-8290.CD-20-0756. Epub 2020 Dec 17. PubMed 33334730
• Locke FL, Rossi JM, Neelapu SS, Jacobson CA, Miklos DB, Ghobadi A, Oluwole OO, Reagan PM, Lekakis LJ, Lin Y, Sherman M, Better M, Go WY, Wiezorek JS, Xue A, Bot A. Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020 Oct 13;4(19):4898-4911. doi: 10.1182/bloodadvances.2020002394. PubMed 33035333
• 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. PubMed 30518502
• 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. PubMed 29226797