RecruitingPhase 3NCT05605899

Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With 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)


Sponsor

Kite, A Gilead Company

Enrollment

300 participants

Start Date

Feb 10, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria8

  • 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.

Exclusion Criteria17

  • 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.

Interventions

BIOLOGICALAxicabtagene Ciloleucel

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

DRUGCyclophosphamide

Administered intravenously

DRUGFludarabine

Administered intravenously

DRUGEtoposide

Administered intravenously

DRUGRituximab

Administered intravenously

DRUGDoxorubicin

Administered intravenously

DRUGVincristine

Administered intravenously

DRUGPrednisone

Administered orally


Locations(90)

University of Alabama Hospital

Birmingham, Alabama, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Mayo Clinic

Phoenix, Arizona, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

University of California Los Angeles (UCLA)

Los Angeles, California, United States

Stanford Cancer Institute

Palo Alto, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

Moffitt Cancer Center

Tampa, Florida, United States

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

The University of Kansas Hospital

Westwood, Kansas, United States

Norton Cancer Institute, St. Matthews Campus

Shelbyville, Kentucky, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

University of MD Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic Cancer Center Outpatient Pharmacy

Rochester, Minnesota, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Weill Cornell Medical College - NewYork Presbyterian Hospital

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Novant Health Cancer Institute- Hematology

Charlotte, North Carolina, United States

Oncology Hematology Care Clinical Trials, LLC

Cincinnati, Ohio, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Prisma Health Cancer Institute

Greenville, South Carolina, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Henry-Joyce Cancer Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

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

Salt Lake City, Utah, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Royal Brisbane and Women's Hospital

South Brisbane, Queensland, Australia

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

Medizinische Universität Innsbruck

Innsbruck, Austria

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

Salzburg, Austria

Universitätsklinikum St. Pölten

Sankt Pölten, Austria

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

Vienna, Austria

Jewish General Hospital

Montreal, Canada

The Ottowa Hospital- General Campus

Ottawa, Canada

Princess Margaret Cancer Centre

Toronto, Canada

CHU Bordeaux-Hopital Haut-Leveque

Bordeaux, France

Centre Leon Berard

Cedex Lyon 08, France

CHU Dijon

Dijon, France

Hopital Claude Huriez CHU Lille, Service Maladies du sang

Lille, France

Hopital Saint Eloi

Montpellier, France

Centre Hospitalier Universitaire de Nice

Nice, France

Hopital Henri MONDOR, APHP

Paris, France

CHU Pontchaillou

Rennes, France

Centre Hospitalier Universitaire(CHU) de Toulouse

Toulouse, France

Helios Klinikum Berlin-Buch

Berlin, Germany

Charite Universitaetsmedizin Berlin

Berlin, Germany

Universitätsklinikum bonn, medizinische klinik III

Bonn, Germany

Uniklinikum Duesseldorf, Klinik fuer Haematologie, Onkologie und klinische Immunologie

Düsseldorf, Germany

Universitätsklinik Erlangen

Erlangen, Germany

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, Italy

ASST Degli Spedali Civili di Brescia

Brescia, Italy

Ospedale San Raffaele

Milan, Italy

Azienda Ospedaliera di Perugia - Ospedale S. Maria della Misericordia

Perugia, Italy

Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, Italy

Universita Cattolica del Sacro Cuore

Rome, Italy

IRCCS Istituto Clinico Humanitas

Rozzano, Italy

University Hospital, Kyoto Prefectural University of Medicine

Kyoto, Japan

Tohoku University Hospital

Miyagi, Japan

Osaka University Hospital

Osaka, Japan

Juntendo University Hospital

Tokyo, Japan

Tokyo Metropolitan Komagome Hospital

Tokyo, Japan

Academisch Medisch Centrum

Amsterdam, Netherlands

University Medical Center Groningen

Groningen, Netherlands

Leiden University Medical Center

Leiden, Netherlands

Maastricht Universitair Medisch Centrum

Maastricht, Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

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

Lisbon, Portugal

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

Lisbon, Portugal

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

Porto, Portugal

Institut Catala d'Oncologia

Barcelona, Spain

Hospital Universitari Vall D'Hebron

Barcelona, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

Hospital Universitario de Salamanca

Salamanca, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Hospital Universitario Virgen del Rocio

Seville, Spain

Hospital Clínico Universitario de Valencia

Valencia, Spain

Addenbrookes Hospital (Cambridge University Hospitals NHS Foundation Trust)

Birmingham, United Kingdom

University Hospitals Southampton

Southampton, United Kingdom

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NCT05605899