Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell Lymphoma (ZUMA-24)

A Phase 2 Open-Label, Multicenter Study Evaluating The Safety And Efficacy of Axicabtagene Ciloleucel Concomitant With Prophylactic Steroids In Subjects With Relapsed Or Refractory Large B-Cell Lymphoma In The Outpatient Setting

The goal of this clinical study is to learn more about the study drug, axicabtagene ciloleucel, in participants with relapsed or refractory large B-cell lymphoma (LBCL) in the outpatient setting.

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Large B-cell Lymphoma
• Intervention / Treatment: Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Dexamethasone

Detailed Description

Participants who complete at minimum 24 months follow up will be transitioned 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 (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Los Angeles, California, United States, 90025
      • UCLA
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Clinical Trials, LLC
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health - Upstate
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
    • Nashville, Tennessee, United States, 37232
      • Henry-Joyce Cancer Clinic
  • Texas
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System of San Antonio
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Healthcare
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute, University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Richmond, Virginia, United States, 23219
      • 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), including the following types defined by World Health Organization (WHO) 2016 classification, by local pathology laboratory assessment, are eligible as defined below:

  • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified.
  • High-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangement.
  • DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV) + DLBCL.
  • Primary mediastinal (thymic) LBCL.
  • Primary cutaneous DLBCL, leg type.
  • Transformation of follicular lymphoma to DLBCL will also be included.
• Relapsed or refractory disease after 1 or more lines of therapy.

• Individuals must have received adequate prior therapy including:

  • Anti-CD20 monoclonal antibody AND
  • An anthracycline-containing chemotherapy regimen.
• At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Individual agrees to outpatient treatment setting and to adhere to the prespecified clinical monitoring requirements.

Key Exclusion Criteria:

• History of autologous or allogeneic stem cell transplant.
• Prior cluster of differentiation (CD)19 targeted therapy.
• Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor.
• Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. DLBCL epidural involvement should be considered as positive CNS disease.
• In the investigator's judgment, the individual is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Axicabtagene Ciloleucel; Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2/day and fludarabine 30 mg/m^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2. Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.

Biological: Axicabtagene Ciloleucel; Administered intravenously; Other Names: Yescarta®; Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Drug: Dexamethasone; Administered orally or intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration		First infusion date of axicabtagene ciloleucel up to 24 months
Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration		First infusion date of axicabtagene ciloleucel up to 24 months
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 72 hours		First infusion date of axicabtagene ciloleucel up to 72 hours
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 7 days		First infusion date of axicabtagene ciloleucel up to 7 days
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 14 days		First infusion date of axicabtagene ciloleucel up to 14 days
Rates of Hospitalization After Axicabtagene ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 30 days		First infusion date of axicabtagene ciloleucel up to 30 days
Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion		First infusion date of axicabtagene ciloleucel up to 24 months
Proportion of Intensive Care Unit (ICU) Admitted Participants		Up to 24 months
Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion		Up to 24 months
Percentage of Participants Experiencing Treatment- Emergent Adverse Events		First infusion date of axicabtagene ciloleucel up to 24 months
Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events		First infusion date of axicabtagene ciloleucel up to 24 months
Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6	The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of 2 components: a descriptive system of the participant's health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. 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, 6 Months
Objective Response Rate (ORR) as Assessed by Investigator Assessment	ORR is defined as the incidence of either a complete response or a partial response by the revised international working group (IWG) response criteria for malignant lymphoma.	Up to 24 months
Complete Response (CR) Rate as Assessed by Investigator Assessment	CR rate is defined as the incident of complete response.	Up to 24 months
Duration of response (DOR) as Assessed by Investigator Assessment	DOR is defined as the time from first objective response to disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause.	Up to 24 months
Progression-free Survival (PFS) as Assessed by Investigator Assessment	PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause.	Up to 24 months
Event Free Survival (EFS) as Assessed by Investigator Assessment	EFS is defined as the time from infusion to the earliest date of disease progression per the revised IWG response criteria for malignant lymphoma, commencement of new anti-lymphoma therapy, or death from any cause.	Up to 24 months
Overall Survival (OS)	OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.	Up to 24 months
Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15		Up to 24 months
Peak Serum Levels of Inflammatory and Immune Modulating Cytokines: IFN-γ, IL-1, IL-6, IL- 13, IL-17, IL-1, IL-1RA, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), Tumor Necrosis Factor-Alpha (TNF-α), and IL-12p40/p70	IFN-γ=Interferon-Gamma, IL-1RA=IL-1 Receptor Antagonist	Up to 24 months
Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin		Up to 24 months
Peak Serum Levels of the Acute Phase Response Proteins: C-Reactive Protein (CRP), Serum Amyloid A (SAA), Soluble IL-2 Receptor Alpha (sIL-1Ra), Ferritin		Up to 24 months
Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time		Up to 24 months
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants 3 Days After Infusion Date		First infusion date of axicabtagene ciloleucel up to 3 days
Peak Serum Levels of Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1)		Up to 24 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Leslie LA, Baird JH, Flinn IW, Tees M, Hoda D, Deol A, Young P, McClune B, Varadarajan I, Essell J, Fanning S, Simmons G, Clark W, Rapoport AP, Rodriguez TE, Winters JN, Davis M, Miao HM, Ray M, Fang X, Kim JJ, Oluwole OO. Outpatient axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma: ZUMA-24 primary analysis. Am J Cancer Res. 2025 Aug 15;15(8):3417-3433. doi: 10.62347/GJNN1023. eCollection 2025.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Actual): November 24, 2025
• Study Completion (Actual): November 24, 2025

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence; Organic Chemicals; Hydrocarbons; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Dexamethasone; Cyclophosphamide; fludarabine; axicabtagene ciloleucel
• Other Study ID Numbers: KT-US-482-0137

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No