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)
概览
- 阶段
- 3 期
- 干预措施
- Prednisone
- 疾病 / 适应症
- High-risk Large B-cell Lymphoma (LBCL)
- 发起方
- Kite, A Gilead Company
- 入组人数
- 300
- 试验地点
- 193
- 主要终点
- Event-free Survival (EFS) by Blinded Central Assessment
- 状态
- 进行中（未招募）
- 最后更新
- 17天前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Prednisone
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.
干预措施: Axicabtagene Ciloleucel
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.
干预措施: Cyclophosphamide
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.
干预措施: Fludarabine
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
干预措施: Cyclophosphamide
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
干预措施: Etoposide
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
干预措施: Rituximab
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
干预措施: Doxorubicin
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
干预措施: Vincristine
结局指标
主要结局
Event-free Survival (EFS) by Blinded Central Assessment
时间窗: 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.
次要结局
- PFS by Investigator Assessment(Up to 5 years)
- Overall Survival(Up to 5 years)
- Progression-free Survival (PFS) by Blinded Central Assessment(Up to 5 years)
- Complete Response (CR) Rate by Blinded Central Assessment(Up to 5 years)
- 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)
- Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values(First dose date up to 5 years plus 30 days)
- 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)
- 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)
- Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score(Baseline, Month 18)