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)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 142
- 主要终点
- Event-free Survival (EFS) by Blinded Central Assessment
研究概览
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
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.
- •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.
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 (Drug)
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 (Biological)
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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)