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Comparing a new treatment to standard care for high-risk large B-cell lymphoma

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)

Phase 3 Interventional Gilead Sciences · NCT05605899

This study is testing a new treatment for high-risk large B-cell lymphoma to see if it works better than the usual therapy for patients who have had just one round of treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment300 (estimated)
Ages18 Years and up
SexAll
SponsorGilead Sciences Industry-sponsored
Drugs / interventionsrituximab, chemotherapy
Locations90 sites (Birmingham, Alabama and 89 other locations)
Trial IDNCT05605899 on ClinicalTrials.gov

What this trial studies

This clinical study aims to evaluate the effectiveness of axicabtagene ciloleucel compared to standard of care therapy in patients with high-risk large B-cell lymphoma. Participants will be randomly assigned to receive either the new treatment or the standard therapy, with follow-up assessments extending over 15 years. The study focuses on patients who have only received one cycle of rituximab plus chemotherapy and have a high-risk disease profile. The goal is to determine if the new treatment can improve outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed high-risk large B-cell lymphoma who have received only one cycle of R-chemotherapy.

Not a fit: Patients with certain subtypes of lymphoma, such as T-cell/histiocyte-rich LBCL or primary DLBCL of the CNS, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective first-line therapy option for patients with high-risk large B-cell lymphoma.

How similar studies have performed: Other studies have shown promising results with CAR T-cell therapies in similar patient populations, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 89 other locations

+40 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions High-risk Large B-cell Lymphoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.