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.

Age: 18 Years and older

Gender: All

Start Date: 02/10/2023

Primary Completion Date (Estimated): 03/01/2031

Study Completion Date (Estimated): 03/01/2031

Accepts Healthy Volunteers: No

Trial Purpose and Description

Five years after randomization, participants who have received axicabtagene ciloleucel will transition to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Eligibility Criteria

Age: 18 Years and older

Gender: All

Accepts Healthy Volunteers: No

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.