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High-risk Large B-cell Lymphoma (LBCL)Phase 3ZUMA-23NCT05605899

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

A Phase 3 study testing Axicabtagene Ciloleucel, Cyclophosphamide and Fludarabine in people with High-risk Large B-cell Lymphoma (LBCL), run by Kite, A Gilead Company at 85 sites in 12 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
High-risk Large B-cell Lymphoma (LBCL)
What is being tested?
Axicabtagene Ciloleucel, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
85 sitesin 12 countries
Study dates
10 Feb 2023to Mar 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 18Show fewer
  • 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.

Trial locations and contacts

85 sites in 12 countries.

85 sites in 12 countries

United States32 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Georgia Cancer Center at Augusta University

    Augusta, Georgia, 30912

  • University of MD Greenebaum Comprehensive Cancer Center

    Baltimore, Maryland, 21201

  • University of Alabama Hospital

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14203

  • Novant Health Cancer Institute- Hematology

    Charlotte, North Carolina, 28204

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60612

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75235

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Prisma Health Cancer Institute

    Greenville, South Carolina, 29615

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • The University of Texas, MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • University of California Los Angeles (UCLA)

    Los Angeles, California, 90095

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • Henry-Joyce Cancer Center

    Nashville, Tennessee, 37232

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Weill Cornell Medical College - NewYork Presbyterian Hospital

    New York, New York, 10021

  • Columbia University Medical Center

    New York, New York, 10032

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Mayo Clinic Cancer Center Outpatient Pharmacy

    Rochester, Minnesota, 55902

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Intermountain LDS Hospital/Blood and Marrow Transplant/ Acute Leukemia Program

    Salt Lake City, Utah, 84143

  • Norton Cancer Institute, St. Matthews Campus

    Shelbyville, Kentucky, 40065

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • The University of Kansas Hospital

    Westwood, Kansas, 66205

Other trials in United States

France9 sites

  • CHU Bordeaux-Hopital Haut-Leveque

    Bordeaux

  • Centre Leon Berard

    Cedex Lyon 08, 69008

  • CHU Dijon

    Dijon, 21079

  • Hopital Claude Huriez CHU Lille, Service Maladies du sang

    Lille, 59037

  • Hopital Saint Eloi

    Montpellier, 34295

  • Centre Hospitalier Universitaire de Nice

    Nice, CS 23079

  • Hopital Henri MONDOR, APHP

    Paris, 94000

  • CHU Pontchaillou

    Rennes, 35033

  • Centre Hospitalier Universitaire(CHU) de Toulouse

    Toulouse, 31100

Other trials in France

Italy7 sites

  • IRCCS Azienda Ospedaliero-Universitaria di Bologna

    Bologna, 40138

  • ASST Degli Spedali Civili di Brescia

    Brescia, 25123

  • Ospedale San Raffaele

    Milan, 20132

  • Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia

    Perugia, 06132

  • Grande Ospedale Metropolitano Bianchi Melacrino Morelli

    Reggio Calabria, 89133

  • Universita Cattolica del Sacro Cuore

    Rome

  • IRCCS Istituto Clinico Humanitas

    Rozzano, 20089

Other trials in Italy

Spain7 sites

  • Institut Catala d'Oncologia

    Barcelona, 08908

  • Hospital Universitari Vall D'Hebron

    Barcelona, 8035

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario Marqués de Valdecilla

    Santander, 39008

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Germany5 sites

  • Helios Klinikum Berlin-Buch

    Berlin, 13125

  • Charite Universitaetsmedizin Berlin

    Berlin

  • Universitätsklinikum bonn, medizinische klinik III

    Bonn, 53127

  • Uniklinikum Duesseldorf, Klinik fuer Haematologie, Onkologie und klinische Immunologie

    Düsseldorf, 40225

  • Universitätsklinik Erlangen

    Erlangen

Other trials in Germany

Japan5 sites

  • University Hospital, Kyoto Prefectural University of Medicine

    Kyoto, 602-8566,

  • Tohoku University Hospital

    Miyagi, 980-8574

  • Osaka University Hospital

    Osaka, 565-0871

  • Juntendo University Hospital

    Tokyo, 113-8431

  • Tokyo Metropolitan Komagome Hospital

    Tokyo, 113-8677

Other trials in Japan

Netherlands5 sites

  • Academisch Medisch Centrum

    Amsterdam, 1081HV

  • University Medical Center Groningen

    Groningen, 9700 RB

  • Leiden University Medical Center

    Leiden, 2333 ZA

  • Maastricht Universitair Medisch Centrum

    Maastricht, 62002

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3508 GA

Other trials in Netherlands

Austria4 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • Zuniklinikum Salzburg, Landeskrankenhaus, Universitatsklinik fur Innere Medizin III der PMU

    Salzburg, 5020

  • Universitätsklinikum St. Pölten

    Sankt Pölten, 3100

  • Medizinische Universität Wien (AKH Wien, Medical University Vienna and General Hospital Vienna)

    Vienna, 01090

Other trials in Austria

Australia3 sites

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Peter MacCallum Cancer Center

    Melbourne, Victoria, 3000

  • Royal Brisbane and Women's Hospital

    South Brisbane, Queensland, 4101

Other trials in Australia

Canada3 sites

  • Jewish General Hospital

    Montreal, H3T1E2

  • The Ottowa Hospital- General Campus

    Ottawa, K1H 8L6

  • Princess Margaret Cancer Centre

    Toronto, M5G 2M9

Other trials in Canada

Portugal3 sites

  • Centro Hospitalar Universitario Lisboa Norte, E.P.E. - Hospital de Santa Maria

    Lisbon

  • Instituto Portugues de Oncologia de Lisboa Francisco Gentil - E.P.E.

    Lisbon

  • Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.

    Porto, 4200-072

Other trials in Portugal

United Kingdom2 sites

  • Addenbrookes Hospital (Cambridge University Hospitals NHS Foundation Trust)

    Birmingham, B15 2TH

  • University Hospitals Southampton

    Southampton, SO16 6YD

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
Axicabtagene Ciloleucel, Cyclophosphamide, Fludarabine, Etoposide, Rituximab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Axicabtagene CiloleucelBiological

    Also called Yescarta®, Axi-cel

    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

  • CyclophosphamideDrug

    Administered intravenously

  • FludarabineDrug

    Administered intravenously

  • EtoposideDrug

    Administered intravenously

  • RituximabDrug

    Administered intravenously

  • DoxorubicinDrug

    Administered intravenously

  • VincristineDrug

    Administered intravenously

  • PrednisoneDrug

    Administered orally

Study groups in NCT05605899
Study groupRoleWhat they receive
Axicabtagene CiloleucelExperimentalParticipants 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.
Receives: Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine
Standard of Care TherapyActive comparatorParticipants 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 1 * Cyclophosphamide 750 mg/m^2 on Day 1 * Doxorubicin 50 mg/m^2 on Day 1 * Vincristine 1.4 mg/m^2 (maximum 2 mg) on Day 1 * Prednisone 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 1 * Etoposide 50 mg/m^2 on Days 1 to 4 * Doxorubicin 10 mg/m^2 on Days 1 to 4 * Vincristine 0.4 mg/m^2 on Days 1 to 4 * Cyclophosphamide 750 mg/m^2 on Day 5 * Prednisone 60 mg/m^2 twice daily on Days 1 to 5
Receives: Drug: Cyclophosphamide; Drug: Etoposide; Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 5 years

Secondary outcomes (9)

  1. 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.

    Measured: Up to 5 years

  2. Overall Survival

    OS is defined as the time from randomization to death due to any cause.

    Measured: Up to 5 years

  3. PFS by Investigator Assessment

    PFS is defined as the time from randomization to disease progression or death due to any cause.

    Measured: Up to 5 years

  4. 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.

    Measured: Up to 5 years

  5. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths

    Measured: First dose date up to 5 years plus 30 days

  6. Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values

    Measured: First dose date up to 5 years plus 30 days

  7. 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.

    Measured: Baseline, Month 18

  8. 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.

    Measured: Baseline, Month 18

  9. 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.

    Measured: Baseline, Month 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2022
  2. Study start10 Feb 2023
  3. Primary completionMar 2031 (estimated)
  4. Study completionMar 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05605899
Sponsor's protocol ID
KT-US-484-0136
Other IDs
2022-501489-24-00
Acronym
ZUMA-23
Status last verified
Apr 2026
First submitted
31 Oct 2022
Last updated
15 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Axicabtagene Ciloleucel, Cyclophosphamide and Fludarabine in people with High-risk Large B-cell Lymphoma (LBCL), run by Kite, A Gilead Company at 85 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 85 sites in United States, France, Italy, Spain, Germany and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (EFS) by Blinded Central Assessment (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05605899.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2026.

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