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RECRUITINGPhase 3INTERVENTIONAL

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)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Key Who May Qualify: - diagnosed by tissue sample (biopsy-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 Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

BIOLOGICAL

Axicabtagene Ciloleucel

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

DRUG

Cyclophosphamide

Administered intravenously

DRUG

Fludarabine

Administered intravenously

DRUG

Etoposide

Administered intravenously

DRUG

Rituximab

Administered intravenously

DRUG

Doxorubicin

Administered intravenously

DRUG

Vincristine

Administered intravenously

DRUG

Prednisone

Administered orally

Locations (20)

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