Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma (ZUMA-23)

An Adaptive Phase 3, Randomized, Open-Label, Multicenter Study to Compare the Efficacy and Safety of Axicabtagene Ciloleucel Versus Standard of Care Therapy as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-23)

The goal of this clinical study is to compare the study drug, axicabtagene ciloleucel, versus standard of care (SOC) in first-line therapy in participants with high-risk large B-cell lymphoma.

Study Overview

• Status: Active, not recruiting
• Conditions: High-risk Large B-cell Lymphoma (LBCL)
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Prednisone; Biological: Axicabtagene Ciloleucel; Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Etoposide

Detailed Description

Five years after randomization, participants who have received axicabtagene ciloleucel will transition to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Center
• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck
  • Salzburg, Austria, 5020
    • zuniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMU
  • Sankt Pölten, Austria, 3100
    • Universitätsklinikum St. Pölten
  • Vienna, Austria, 01090
    • Medizinische Universität Wien (AKH Wien, Medical University Vienna and General Hospital Vienna)
• Canada
  • Montreal, Canada, H3T1E2
    • Jewish General Hospital
  • Ottawa, Canada, K1H 8L6
    • The Ottowa Hospital- General Campus
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Cancer Centre
• France
  • Bordeaux, France
    • CHU Bordeaux-Hopital Haut-Leveque
  • Cedex Lyon 08, France, 69008
    • Centre Leon Berard
  • Dijon, France, 21079
    • CHU Dijon
  • Lille, France, 59037
    • Hopital Claude Huriez CHU Lille, Service Maladies du sang
  • Montpellier, France, 34295
    • Hopital Saint Eloi
  • Nice, France, CS 23079
    • Centre Hospitalier Universitaire de Nice
  • Paris, France, 94000
    • Hopital Henri MONDOR, APHP
  • Rennes, France, 35033
    • Chu Pontchaillou
  • Toulouse, France, 31100
    • Centre Hospitalier Universitaire(CHU) de Toulouse
• Germany
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Berlin, Germany
    • Charité Universitaetsmedizin Berlin
  • Bonn, Germany, 53127
    • Universitätsklinikum bonn, medizinische klinik III
  • Düsseldorf, Germany, 40225
    • Uniklinikum Duesseldorf, Klinik fuer Haematologie, Onkologie und klinische Immunologie
  • Erlangen, Germany
    • Universitätsklinik Erlangen
• Italy
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna
  • Brescia, Italy, 25123
    • Asst Degli Spedali Civili Di Brescia
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Perugia, Italy, 06132
    • Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia
  • Reggio Calabria, Italy, 89133
    • Grande Ospedale Metropolitano Bianchi Melacrino Morelli
  • Rome, Italy
    • Università Cattolica del Sacro Cuore
  • Rozzano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
• Japan
  • Kyoto, Japan, 602-8566,
    • University Hospital, Kyoto Prefectural University of Medicine
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Komagome Hospital
• Netherlands
  • Amsterdam, Netherlands, 1081HV
    • Academisch Medisch Centrum
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Maastricht, Netherlands, 62002
    • Maastricht Universitair Medisch Centrum
  • Utrecht, Netherlands, 3508 GA
    • Universitair Medisch Centrum Utrecht
• Portugal
  • Lisbon, Portugal
    • Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria
  • Lisbon, Portugal
    • Instituto Portugues de Oncologia de Lisboa Francisco Gentil - E.P.E.
  • Porto, Portugal, 4200-072
    • Instituto Português de Oncologia do Porto Francisco Gentil, E.P.E.
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08908
    • Institut Catala d'Oncologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Salamanca, Spain, 37007
    • Hospital Universitario De Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Addenbrookes Hospital (Cambridge University Hospitals NHS Foundation Trust)
  • Southampton, United Kingdom, SO16 6YD
    • University Hospitals Southampton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60612
      • Northwestern Memorial Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Hospital
  • Kentucky
    • Shelbyville, Kentucky, United States, 40065
      • Norton Cancer Institute, St. Matthews Campus
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of MD Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Cancer Center Outpatient Pharmacy
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - NewYork Presbyterian Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute- Hematology
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Intermountain LDS Hospital/Blood and Marrow Transplant/ Acute Leukemia Program
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:

  • Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
  • High-grade B-cell lymphoma (HGBL)
• Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen.
• High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.
• Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).
• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
• Females of childbearing potential must have a negative serum or urine pregnancy test.

Key Exclusion Criteria:

• The following WHO 2016 subcategories by local assessment:

  • T-cell/histiocyte-rich LBCL
  • Primary DLBCL of the central nervous system (CNS)
  • Primary mediastinal (thymic) LBCL
  • B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
  • Burkitt lymphoma
  • History of Richter's transformation of chronic lymphocytic leukemia
• Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.
• Presence of cardiac lymphoma involvement.
• Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Presence of CNS disorder. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.
• History of acute or chronic active hepatitis B or C infection.
• Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count > 200 cells/uL.
• Medical conditions or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.
• History of clinically significant cardiac disease within 12 months before enrollment.
• History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axicabtagene Ciloleucel; Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: Axicabtagene Ciloleucel; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells; Other Names: Yescarta®; Axi-cel
Active Comparator: Standard of Care Therapy; Participants will receive the investigator's choice of one of the following therapies/dosing schedules: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for a total of 6 cycles (21-day cycle)Rituximab 375 mg/m^2 on Day 1Cyclophosphamide 750 mg/m^2 on Day 1Doxorubicin 50 mg/m^2 on Day 1Vincristine 1.4 mg/m^2 (maximum 2 mg) on Day 1Prednisone 40 mg/m^2 on Day 1 through Day 5; Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for a total of 6 cycles (21-day cycle)Rituximab 375 mg/m^2 on Day 1Etoposide 50 mg/m^2 on Days 1 to 4Doxorubicin 10 mg/m^2 on Days 1 to 4Vincristine 0.4 mg/m^2 on Days 1 to 4Cyclophosphamide 750 mg/m^2 on Day 5Prednisone 60 mg/m^2 twice daily on Days 1 to 5	Drug: Cyclophosphamide; Administered intravenously; Drug: Prednisone; Administered orally; Drug: Rituximab; Administered intravenously; Drug: Doxorubicin; Administered intravenously; Drug: Vincristine; Administered intravenously; Drug: Etoposide; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival (EFS) by Blinded Central Assessment	EFS, is defined as the time from randomization to the earliest occurrence of death due to any cause, disease progression/relapse, initiation of any non-protocol specified subsequent new lymphoma therapy for the treatment of residual disease or Biopsy-proven residual disease at the Month 6 disease assessment or later, regardless of whether subsequent new lymphoma therapy is initiated or not.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS is defined as the time from randomization to death due to any cause.	Up to 5 years
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths		First dose date up to 5 years plus 30 days
Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values		First dose date up to 5 years plus 30 days
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Hodgkin Lymphoma High Grade Module (EORTC QLQ-NHL-HG29) Score	The EORTC QLQ-NHL-HG29 is a 29-item patient-reported assessment measuring patients' high-grade NHL-specific symptoms and functioning. The 29 items assess symptom burden due to disease and/or treatment, fatigue/physical condition, neuropathy, emotional impacts, and worries/fears health and functioning. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, Month 18
Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.	Baseline, Month 18
Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score	The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) symptom single-item scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.	Baseline, Month 18
Progression-free Survival (PFS) by Blinded Central Assessment	PFS is defined as the time from randomization to disease progression or death due to any cause.	Up to 5 years
PFS by Investigator Assessment	PFS is defined as the time from randomization to disease progression or death due to any cause.	Up to 5 years
Complete Response (CR) Rate by Blinded Central Assessment	CR rate is defined as the proportion of participants who have achieved CR per Lugano classification after treatment completion and prior to subsequent new off protocol anti-lymphoma therapy.	Up to 5 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2023
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Alkaloids; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Indoles; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Aminoglycosides; Antibodies, Monoclonal, Murine-Derived; Daunorubicin; Rituximab; Prednisone; Cyclophosphamide; Etoposide; Doxorubicin; Vincristine; fludarabine; axicabtagene ciloleucel
• Other Study ID Numbers: KT-US-484-0136; 2022-501489-24-00 (Other Identifier: European Medicines Agency)

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