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

Sponsor
Kite, A Gilead Company (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05605899
Collaborator
(none)
300
2
96.9

Study Details

Study Description

Brief Summary

The goal of this study is to find out if the experimental product, axi-cel, is safe and effective in treating your lymphoma, compared to standard of care (SOC) therapy), which includes either R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) or DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab).

Detailed Description

Five years after the last study participant is randomized, 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.

Study Design

Study Type:
Interventional
Anticipated 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)
Anticipated Study Start Date :
Feb 1, 2023
Anticipated Primary Completion Date :
Mar 1, 2031
Anticipated Study Completion Date :
Mar 1, 2031

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Event-free Survival (EFS) by Central Assessment [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 Investigator Assessment [Up to 5 years]

      PFS is defined as the time from randomization to disease progression or death due to any cause.

    2. Overall Survival [Up to 5 years]

      OS is defined as the time from randomization to death due to any cause.

    3. PFS by Central Assessment [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 Central Assessment [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 [First dose date up to 5 years plus 30 days]

    6. Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values [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 [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 [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 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • 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 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.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Kite, A Gilead Company

    Investigators

    • Study Director: Kite Study Director, Kite, A Gilead Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Kite, A Gilead Company
    ClinicalTrials.gov Identifier:
    NCT05605899
    Other Study ID Numbers:
    • KT-US-484-0136
    • 2022-501489-24-00
    First Posted:
    Nov 4, 2022
    Last Update Posted:
    Dec 15, 2022
    Last Verified:
    Dec 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 15, 2022