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

NCT05605899 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: KT-US-484-01362022-501489-24-00
• Study Type: interventional
• Target: 300
• Locations: 11 countries
• Sites: 81

Brief 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.

Conditions

High-risk Large B-cell Lymphoma (LBCL)

Outcome Measures

Primary Outcomes (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.

  Up to 5 years

Secondary Outcomes (9)

• Progression-free Survival (PFS) by Blinded Central Assessment

  Up to 5 years

• Overall Survival

  Up to 5 years

• PFS by Investigator Assessment

  Up to 5 years

• Complete Response (CR) Rate by Blinded Central Assessment

  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

Study Arms (2)

Axicabtagene Ciloleucel

EXPERIMENTAL

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.

Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Standard of Care Therapy

ACTIVE COMPARATOR

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 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

Drug: Cyclophosphamide; Drug: Etoposide; Drug: Rituximab; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Interventions

Cyclophosphamide DRUG

Administered intravenously

Axicabtagene Ciloleucel; Standard of Care Therapy

Fludarabine DRUG

Administered intravenously

Axicabtagene Ciloleucel

Etoposide DRUG

Administered intravenously

Standard of Care Therapy

Rituximab DRUG

Administered intravenously

Standard of Care Therapy

Doxorubicin DRUG

Administered intravenously

Standard of Care Therapy

Vincristine DRUG

Administered intravenously

Standard of Care Therapy

Prednisone DRUG

Administered orally

Standard of Care Therapy

Axicabtagene Ciloleucel BIOLOGICAL

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

Also known as: Yescarta®, Axi-cel

Axicabtagene Ciloleucel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (85)

University of Alabama Hospital

Birmingham, Alabama, 35233, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

The University of Kansas Hospital

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute, St. Matthews Campus

Shelbyville, Kentucky, 40065, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of MD Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Cancer Center Outpatient Pharmacy

Rochester, Minnesota, 55902, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

Weill Cornell Medical College - NewYork Presbyterian Hospital

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Novant Health Cancer Institute- Hematology

Charlotte, North Carolina, 28204, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29615, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Henry-Joyce Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

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

Salt Lake City, Utah, 84143, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Royal Brisbane and Women's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

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

Salzburg, 5020, Austria

Location

Universitätsklinikum St. Pölten

Sankt Pölten, 3100, Austria

Location

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

Vienna, 01090, Austria

Location

Jewish General Hospital

Montreal, H3T1E2, Canada

Location

The Ottowa Hospital- General Campus

Ottawa, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

Location

CHU Bordeaux-Hopital Haut-Leveque

Bordeaux, France

Location

Centre Leon Berard

Cedex Lyon 08, 69008, France

Location

CHU Dijon

Dijon, 21079, France

Location

Hopital Claude Huriez CHU Lille, Service Maladies du sang

Lille, 59037, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Centre Hospitalier Universitaire de Nice

Nice, CS 23079, France

Location

Hopital Henri MONDOR, APHP

Paris, 94000, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Centre Hospitalier Universitaire(CHU) de Toulouse

Toulouse, 31100, France

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Charite Universitaetsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum bonn, medizinische klinik III

Bonn, 53127, Germany

Location

Uniklinikum Duesseldorf, Klinik fuer Haematologie, Onkologie und klinische Immunologie

Düsseldorf, 40225, Germany

Location

Universitätsklinik Erlangen

Erlangen, Germany

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, 40138, Italy

Location

ASST Degli Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia

Perugia, 06132, Italy

Location

Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, 89133, Italy

Location

Universita Cattolica del Sacro Cuore

Rome, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

University Hospital, Kyoto Prefectural University of Medicine

Kyoto, 602-8566,, Japan

Location

Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Tokyo Metropolitan Komagome Hospital

Tokyo, 113-8677, Japan

Location

Academisch Medisch Centrum

Amsterdam, 1081HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Maastricht Universitair Medisch Centrum

Maastricht, 62002, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3508 GA, Netherlands

Location

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

Lisbon, Portugal

Location

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

Lisbon, Portugal

Location

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

Porto, 4200-072, Portugal

Location

Institut Catala d'Oncologia

Barcelona, 08908, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 8035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Addenbrookes Hospital (Cambridge University Hospitals NHS Foundation Trust)

Birmingham, B15 2TH, United Kingdom

Location

University Hospitals Southampton

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

axicabtagene ciloleucel; Cyclophosphamide; fludarabine; Etoposide; Rituximab; Doxorubicin; Vincristine; Prednisone

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 4, 2022
• Study Start: February 10, 2023
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5); JP (5); PT (3); FR (9); AU (3); NL (5); ES (7); GB (2); US (32); CA (3); IT (7)