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

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

  • High-risk Large B-cell Lymphoma (LBCL)

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.