Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma (ZUMA-23)

Gilead Sciences

Status and phase

Enrolling

Phase 3

Conditions

High-risk Large B-cell Lymphoma (LBCL)

Treatments

Drug: Rituximab

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Etoposide

Biological: Axicabtagene Ciloleucel

Drug: Vincristine

Drug: Prednisone

Drug: Fludarabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT05605899

KT-US-484-0136

2022-501489-24-00 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

300 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

300 participants in 2 patient groups

Axicabtagene Ciloleucel

Experimental group

Description:

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.

Treatment:

Drug: Fludarabine

Biological: Axicabtagene Ciloleucel

Drug: Cyclophosphamide

Standard of Care Therapy

Active Comparator group

Description:

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

Treatment:

Drug: Prednisone

Drug: Vincristine

Drug: Etoposide

Drug: Doxorubicin

Drug: Cyclophosphamide

Drug: Rituximab