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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Axicabtagene Ciloleucel 		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.
  • Biological: Axicabtagene Ciloleucel
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
    Other names:
    • Yescarta®
    • Axi-cel
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Active Comparator
Standard of Care Therapy 		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
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Etoposide
    Administered intravenously
  • Drug: Rituximab
    Administered intravenously
  • Drug: Doxorubicin
    Administered intravenously
  • Drug: Vincristine
    Administered intravenously
  • Drug: Prednisone
    Administered orally

Recruiting Locations

The University of Kansas Hospital
Westwood, Kansas 66205

More Details

Status
Recruiting
Sponsor
Kite, A Gilead Company

Study Contact

Medical Information
844-454-5483(1-844-454-KITE)
medinfo@kitepharma.com

Detailed 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.