Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2) (ZUMA-2)

• ClinicalTrials.gov Identifier: NCT02601313
• Recruitment Status: Completed
• First Posted: November 10, 2015
• Results First Posted: September 10, 2020
• Last Update Posted: February 12, 2024
• Sponsor: Kite, A Gilead Company
• Information provided by (Responsible Party): Gilead Sciences ( Kite, A Gilead Company )

Study Description

Brief Summary:

The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).

Condition or disease	Intervention/treatment	Phase
Relapsed/Refractory Mantle Cell Lymphoma	Biological: brexucabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Axicabtagene Ciloleucel	Phase 2

Detailed Description:

Study KTE-C19-102 enrolled participants with r/r MCL who have been treated with up to 5 prior regimens including a Bruton's tyrosine kinase inhibitor (BTKi) in Cohort 1 and Cohort 2. However, to fulfill FDA Postmarketing Requirement, Cohort 3 is added to the study. It will include participants with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi.

The primary analysis in Cohort 1 and Cohort 2 is already completed. Data for Cohort 3 will be analyzed separately. Therefore, details for Cohort 3 were registered separately (NCT04880434) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma
• Actual Study Start Date: November 9, 2015
• Actual Primary Completion Date: July 24, 2019
• Actual Study Completion Date: September 22, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19); Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 CAR T cells/kg, with a maximum dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.

Biological: brexucabtagene autoleucel; A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells; Other Name: KTE-X19, TECARTUS™; Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Drug: Axicabtagene Ciloleucel; A single infusion of axicabtagene ciloleucel anti-CD 19 CAR T cells

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1 [ Time Frame: Up to 2 years ]
   OR: complete metabolic response(CMR),complete radiological response(CRR),partial MR response(PMR),partial RR(PRR).CMR:score 1(no uptake above background)/2(uptake ≤ mediastinum)/3(uptake > mediastinum but ≤ liver)with/without a residual mass on positron emission tomography 5-point scale;no new lesions.CRR:target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion(LDi);no extralymphatic sites of disease;absent non-measured lesion(NMLs);organ enlargement regress to normal;no new sites;bone marrow normal by morphology. PMR:score 4(uptake moderately > liver)/5(uptake markedly > liver, new lesions)with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment (EOT).PRR: ≥ 50% decrease in sum of the product of the diameters(SPD)of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by > 50% in length beyond normal.
2. Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 2 [ Time Frame: Up to 2 years ]
   OR: CMR, CRR, PMR, PRR. CMR: score 1(no uptake above background) / 2(uptake ≤ mediastinum) / 3(uptake > mediastinum but ≤ liver) with/without a residual mass on positron emission tomography 5-point scale; no new lesions. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in LDi; no extralymphatic sites of disease;absent non-measured lesion NMLs; organ enlargement regress to normal; no new sites; bone marrow normal by morphology. PMR: score 4(uptake moderately > liver) /5 (uptake markedly > liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at EOT. PRR: ≥ 50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by > 50% in length beyond normal.

Secondary Outcome Measures :

1. Duration of Response (DOR) in Cohort 1 [ Time Frame: Up to 15 years ]
   DOR: time from the first OR to progressive disease (PD)/death. It is determined using Kaplan-Meier (KM) estimates. PD: score 4 (uptake moderately > liver)/ 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma at interim/EOT assessment; new FDG-avid foci consistent with lymphoma rather than another etiology; new/recurrent FDG-avid foci in bone marrow; an individual node/lesion must be abnormal with: LDi > 1.5 cm, increase by ≥ 50% from cross-product of LDi and perpendicular diameter (PPD) nadir, increase in LDi or shortest axis perpendicular to the LDi from nadir, the splenic length must increase by > 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, the increase must be ≥ 2 cm from baseline; new/recurrent splenomegaly; new or clear progression of pre-existing NMLs; new lesion; new/recurrent bone marrow involvement.
2. Duration of Response (DOR) in Cohort 2 [ Time Frame: Up to 15 years ]
   DOR: time from the first OR to PD/death. It is determined using KM estimates. PD: score 4 (uptake moderately > liver)/5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim/EOT assessment; new FDG-avid foci consistent with lymphoma rather than another etiology; new/recurrent FDG-avid foci in bone marrow; an individual node/lesion must be abnormal with: LDi > 1.5 cm, increase by ≥ 50% from cross-product of LDi and PPD nadir, increase in LDi or shortest axis perpendicular to the LDi from nadir, the splenic length must increase by > 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, the increase must be ≥ 2 cm from baseline; new/recurrent splenomegaly; new or clear progression of pre-existing NMLs; new lesion; new/recurrent bone marrow involvement.
3. Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1 [ Time Frame: Up to 15 years ]
   BOR consists of (Complete response [CR], Partial response [PR], stable disease [SD], progressive disease [PD] and unknown). CR: disappearance of all detectable clinical evidence; PR: 50% decrease in the sum of the product of diameters (SPD) of up to 6 largest dominant nodal masses and >= 50% decrease in SPD of spleen/liver nodules; PD: appearance of any new lesions or >= 50% increase in SPD of more than one node or >= 50% increase in longest diameter of a previously identified node or >50% increase from nadir in the SPD of any previous lesions; SD: failure to attain CR/PR or PD.
4. Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2 [ Time Frame: Up to 15 years ]
   BOR consists of CR (CMR/CRR), PR (PMR/PRR), SD, PD and not done. CMR/CRR and PMR/PRR are defined in Outcome Measure (OM) 1. PD is defined in OM 3. SD/no metabolic response (NMR): a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/ or new lesions) with no significant change in FDG uptake compared to baseline (screening), at an interim time point or end of treatment; no new sites of disease should be observed.Not done: no assessment at the time of analysis.
5. Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1 [ Time Frame: Up to 15 years ]
   OR: CR or PR. CR: disappearance of all detectable clinical evidence; typically FDG-avid lymphoma (a post-treatment residual mass of any size is permitted if it is PET negative); variably FDG-avid lymphomas/FDG avidity unknown (all lymph nodes and nodal masses must have regressed to normal size); spleen and/or liver should be normal size and not be palpable; bone marrow aspirate and biopsy must show no evidence of disease. PR: 50% decrease in the SPD of up to 6 largest dominant nodal masses and ≥ 50% decrease in SPD of spleen/liver nodules; no increase in size of nodes, liver, or spleen and no new sites of disease; splenic and hepatic nodules must regress by ≥ 50% in the SPD; if participant has persistent bone marrow involvement and otherwise meets criteria for CR, will then be considered a PR; typically FDG-avid lymphoma (the post-treatment PET scan should be positive in at least 1 previously involved site.
6. Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2 [ Time Frame: Up to 15 years ]
   OR: CMR, CRR, PMR, PRR. CMR: score 1(no uptake above background) / 2(uptake ≤ mediastinum) / 3(uptake > mediastinum but ≤ liver) with/without a residual mass on positron emission tomography 5-point scale; no new lesions. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in LDi ;no extralymphatic sites of disease;absent NMLs; organ enlargement regress to normal; no new sites;bone marrow normal by morphology. PMR: score 4 (uptake moderately > liver) /5 (uptake markedly > liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at EOT. PRR: ≥ 50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs; spleen regressed by > 50% in length beyond normal.
7. Progression Free Survival (PFS) in Cohort 1 [ Time Frame: Up to 15 years ]
   PFS was defined as the time from the brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD: a score 4 (uptake moderately > liver) or 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. PFS was determined using the KM estimates.
8. Progression Free Survival (PFS) in Cohort 2 [ Time Frame: Up to 15 years ]
   PFS was defined as the time from the brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD: a score 4 (uptake moderately > liver) or 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. PFS was determined using the KM estimates.
9. Overall Survival in Cohort 1 [ Time Frame: Up to 15 years ]
   Overall survival was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Overall survival was determined using the KM estimates.
10. Overall Survival in Cohort 2 [ Time Frame: Up to 15 years ]
    Overall survival was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Overall survival was determined using the KM estimates.
11. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 15 years ]
12. Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade [ Time Frame: Up to 15 years ]
13. Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade [ Time Frame: Up to 15 years ]
14. Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade [ Time Frame: Up to 15 years ]
15. Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade [ Time Frame: Up to 15 years ]
16. Percentage of Participants With Anti-CD19 CAR Antibodies [ Time Frame: Up to 15 years ]
17. Peak Anti-CD19 CAR T-Cell (Brexucabtagene Autoleucel) Level (Maximum Observed Plasma Concentration) in Blood [ Time Frame: Up to 15 years ]
18. Peak Serum Levels of C-Reactive Protein (CRP) in Blood [ Time Frame: Up to 15 years ]
19. Peak Serum Levels of C-X-C Motif Chemokine 10 (CXCL10), Granzyme B, Interferon-Gamma (IFN-γ), Interleukin-1 Receptor Antagonist (IL-1RA), Interleukin (IL)-2, IL-6, IL-7, IL-8,IL-10, IL-15, and Tumor Necrosis Factor-Alpha (TNF-α) in Blood [ Time Frame: Up to 15 years ]
20. Peak Serum Levels of Ferritin, Interleukin-2 Receptor Alpha (IL-2Rα), Intercellular Adhesion Molecule-1 (ICAM-1), Perforin, Vascular Cell Adhesion Molecule-1 (VCAM-1) in Blood [ Time Frame: Up to 15 years ]
21. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Mobility Scale Score [ Time Frame: Baseline, Week 4, Month 3, and Month 6 ]
    The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. The percentage of participants with each level of problem are reported.
22. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Self-Care Scale Score [ Time Frame: Baseline, Week 4, Month 3, and Month 6 ]
    The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. The percentage of participants with each level of problem are reported.
23. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Usual Activity Scale Score [ Time Frame: Baseline, Week 4, Month 3, and Month 6 ]
    The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. The percentage of participants with each level of problem are reported.
24. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Pain / Discomfort Activity Scale Score [ Time Frame: Baseline, Week 4, Month 3, and Month 6 ]
    The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. The percentage of participants with each level of problem are reported.
25. Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Anxiety / Depression Activity Scale Score [ Time Frame: Baseline, Week 4, Month 3, and Month 6 ]
    The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. The Percentage of participants with each level of problem are reported.
26. Change Over Time in EQ-5D Visual Analogue Scale (VAS) Score [ Time Frame: Baseline, Week 4, Month 3, and Month 6 ]
    EQ-5D is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ5D-VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicates better self-reported health status. A positive change indicates an improvement.

Eligibility Criteria

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

Criteria

Key Inclusion Criteria:

Up to 5 prior regimens for MCL. Prior therapy must have included:

• Anthracycline or bendamustine-containing chemotherapy and
• Anti-CD20 monoclonal antibody therapy and
• Ibrutinib or acalabrutinib

At least 1 measurable lesion

Platelet count ≥ 75,000/uL

Creatinine clearance (as estimated by Cockcroft Gault) > or = to 60 mL/min

Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings

Baseline oxygen saturation >92% on room air.

Key Exclusion Criteria:

• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per standard serological and genetic testing
• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson

Gilbert, Arizona, United States, 85234

United States, California

City of Hope

Duarte, California, United States, 91010

University California Los Angeles (UCLA)

Santa Monica, California, United States, 90404

Stanford University

Stanford, California, United States, 94305

United States, Colorado

Sarah Cannon

Denver, Colorado, United States, 80218

United States, Florida

University of Miami

Miami, Florida, United States, 33136

H Lee Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Georgia

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

Loyola University Chicago

Maywood, Illinois, United States, 60153

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

University of Rochester Medical Center

Rochester, New York, United States, 14642

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Ohio State University

Columbus, Ohio, United States, 43210

United States, Oregon

Robert W. Franz Cancer Research Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States, 75246

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98104

France

Centre Hospitalier Universitaire (CHU)

Bordeaux, France

Hospital Saint Louis

Paris, France, 75010

Hopital Haut-Leveque

Pessac, France, 44035

Germany

Universitätsklinik Dresden

Dresden, Germany, 01307

Universitaetsklinikum Wuerzburg

Wuerzburg, Germany, 97080

Netherlands

Academisch Medisch Centrum

Amsterdam, Netherlands

University Medical Center Groningen

Groningen, Netherlands

Erasmus Medical Center

Rotterdam, Netherlands

Sponsors and Collaborators

Kite, A Gilead Company

Investigators

• Study Director: Kite Study Director; Kite, A Gilead Company

  Study Documents (Full-Text)

Documents provided by Gilead Sciences ( Kite, A Gilead Company ):

Study Protocol  [PDF] October 29, 2018

Statistical Analysis Plan  [PDF] July 8, 2019

More Information

Additional Information:

Gilead Clinical Trials Website 

Publications of Results:

Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.

Locke F, Wang M, Siddiqi T, Castro J, Shah B, Lee H, et al. ZUMA-2: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-C19 (Anti-CD19 CAR T cells) in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL). American Society Of Clinical Oncology (ASCO) Annual Meeting 2016.

Wang M, Locke F, Siddiqi T, Castro J, Shah B, Lee H, et al. ZUMA-2: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-C19 (Anti-CD19 CAR T cells) in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL). European Society for Medical Oncology (ESMO) Congress 2016;Abstract 3305

Wang M, Locke FL, Munoz J, Goy A, Holmes HE, Siddiqi T, et al. ZUMA-2: Phase 2 Multicenter Study Evaluating Efficacy of Kte-C19 in Patients with Relapsed/Refractory Mantle Cell Lymphoma [Abstract]. J Clin Oncol 2018;36 (Suppl 15):TPS3102.

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.

Wang, Michael; Rossi, John M.; Munoz, Javier; Goy, Andre; Lundry Locke, Frederick; Michael Reagan, Patrick; Jacobson, Caron A.; Hill, Brian T; Holmes, Houston; Mary Jaglowski, Samantha; Peng, Weimin; Zheng, Lianqing; Fang, Xiang; Xue, Allen; Rao, Arati V.; Bot, Adrian

Wang, Michael(1); Munoz, Javier(2); Goy, Andre(3); Locke, Frederick L.(4); Jacobson, Caron A.(5); Hill, Brian T.(6); Timmerman, John M.(7); Holmes, Houston(8); Jaglowski, Samantha(9); Flinn, Ian W.(10); McSweeney, Peter A.(11); Miklos, David B.(12); Pagel, John M.(13); José Kersten, Marie(14); Peng, Weimin(15); Zheng, Lianqing(15); Rossi, John M.(15); Jain, Rajul K.(15); Rao, Arati V.(15); Reagan, Patrick M.(16)

Wang, M.(1); Munoz, J.(2); Goy, A.(3); Locke, F.(4); Jacobson, C.(5); Hill, B.(6); Timmerman, J.(7); Holmes, H.(8); Jaglowski, S.(9); Flinn, I.(10); McSweeney, P.(11); Miklos, D.(12); Pagel, J.(13); Kersten, M. J.(14)(15)

Michael Wang,1 Javier Munoz,2 Andre Goy,3 Frederick L. Locke,4 Caron A. Jacobson,5 Brian T. Hill,6 John M. Timmerman,7 Houston Holmes,8 Samantha Jaglowski,9 Ian W. Flinn,10 Peter A. McSweeney,11 David B. Miklos,12 John M. Pagel,13 Marie José Kersten,14 Noel Milpied,15 Henry Fung,16 Max S. Topp,17 Roch Houot,18 Amer Beitinjaneh,19 Weimin Peng,20 Lianqing Zheng,20 John M. Rossi,20 Rajul K. Jain,20 Arati V. Rao,20 and Patrick M. Reagan21

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, Peng W,Zheng L,Rossi JM, Jain RK, Rao AV, Reagan PM

Wang, Michael L., MD(1); Munoz, Javier, MD(2); Goy, Andre, MD(3); Locke, Frederick L., MD(4); Jacobson, Caron A., MD, MMSc(5); Hill, Brian T., MD(6); Timmerman, John M., MD(7); Holmes, Houston, MD(8); Jaglowski, Samantha, MD, MPH(9); Flinn, Ian W., MD, PhD(10); McSweeney, Peter A., MD(11); Miklos, David B., MD, PhD(12); Pagel, John M., MD, PhD, DSc(13); Jose Kersten, Marie, MD, PhD(14); Peng, Weimin, MS(15); Zheng, Lianqing, PhD(15); Rossi, John M., MS(15); Jain, Rajul K., MD(15); Rao, Arati V., MD(15); Reagan, Patrick M, MD(16)

Wang, Michael; Lundry Locke, Frederick; Munoz, Javier; Goy, Andre; Eccleston Holmes, Houston; Siddiqi, Tanya; Flinn, Ian; McSweeney, Peter A; Michael Reagan, Patrick; Thomas Hill, Brian; Jacobson, Caron A.; Rizzieri, David A.; Heffner, Leonard T.; Mary Jaglowski, Samantha; Bernard Miklos, David; Shaughnessy, Paul; Unabia, Sherry; Rossi, John M.; Jiang, Yizhou; Jain, Rajul K.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wang M, Jain P, Chi TL, Chen SE, Heimberger A, Weathers SP, Zheng L, Rao AV, Rossi JM. Management of a patient with mantle cell lymphoma who developed severe neurotoxicity after chimeric antigen receptor T-cell therapy in ZUMA-2. J Immunother Cancer. 2020 Oct;8(2):e001114. doi: 10.1136/jitc-2020-001114.

• Responsible Party: Kite, A Gilead Company
• ClinicalTrials.gov Identifier: NCT02601313
• Other Study ID Numbers: KTE-C19-102; 2015-005008-27 ( EudraCT Number ); 2023-506641-35 ( Other Identifier: European Medicines Agency )
• First Posted: November 10, 2015
• Results First Posted: September 10, 2020
• Last Update Posted: February 12, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Mantle-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Fludarabine; Axicabtagene ciloleucel; Brexucabtagene autoleucel; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological