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

Protocol # :
High-risk Large B-cell Lymphoma (LBCL)
Disease Sites
Non-Hodgkin's Lymphoma
Principal Investigator
Jacobson, Caron, A

Trial Description

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 Requirements

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

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

- 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.