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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)

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ClinicalTrials.gov Identifier: NCT05605899
Recruitment Status : Recruiting
First Posted : November 4, 2022
Last Update Posted : June 17, 2024
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Brief 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.

Condition or disease Intervention/treatment Phase
High-risk Large B-cell Lymphoma (LBCL) Biological: Axicabtagene Ciloleucel Drug: Cyclophosphamide Drug: Fludarabine Drug: Etoposide Drug: Rituximab Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 (ZUMA-23)
Actual Study Start Date : February 10, 2023
Estimated Primary Completion Date : March 2031
Estimated Study Completion Date : March 2031

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Event-free Survival (EFS) by Blinded Central Assessment [ Time Frame: Up to 5 years ]
    EFS, is defined as the time from randomization to the earliest occurrence of death due to any cause, disease progression/relapse, initiation of any non-protocol specified subsequent new lymphoma therapy for the treatment of residual disease or Biopsy-proven residual disease at the Month 6 disease assessment or later, regardless of whether subsequent new lymphoma therapy is initiated or not.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) by Blinded Central Assessment [ Time Frame: Up to 5 years ]
    PFS is defined as the time from randomization to disease progression or death due to any cause.

  2. Overall Survival [ Time Frame: Up to 5 years ]
    OS is defined as the time from randomization to death due to any cause.

  3. PFS by Investigator Assessment [ Time Frame: Up to 5 years ]
    PFS is defined as the time from randomization to disease progression or death due to any cause.

  4. Complete Response (CR) Rate by Blinded Central Assessment [ Time Frame: Up to 5 years ]
    CR rate is defined as the proportion of participants who have achieved CR per Lugano classification after treatment completion and prior to subsequent new off protocol anti-lymphoma therapy.

  5. Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths [ Time Frame: First dose date up to 5 years plus 30 days ]
  6. Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values [ Time Frame: First dose date up to 5 years plus 30 days ]
  7. Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score [ Time Frame: Baseline, Month 18 ]
    The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) symptom single-item scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.

  8. Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Hodgkin Lymphoma High Grade Module (EORTC QLQ-NHL-HG29) Score [ Time Frame: Baseline, Month 18 ]
    The EORTC QLQ-NHL-HG29 is a 29-item patient-reported assessment measuring patients' high-grade NHL-specific symptoms and functioning. The 29 items assess symptom burden due to disease and/or treatment, fatigue/physical condition, neuropathy, emotional impacts, and worries/fears health and functioning. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.

  9. Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score [ Time Frame: Baseline, Month 18 ]
    The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05605899


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

Locations
Show Show 65 study locations
Sponsors and Collaborators
Kite, A Gilead Company
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company
Additional Information:
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Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT05605899    
Other Study ID Numbers: KT-US-484-0136
2022-501489-24-00 ( Other Identifier: European Medicines Agency )
First Posted: November 4, 2022    Key Record Dates
Last Update Posted: June 17, 2024
Last Verified: June 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Fludarabine
Etoposide
Vincristine
Axicabtagene ciloleucel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors