A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 14
- 主要终点
- Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators
研究概览
简要总结
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.
详细描述
Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Chemotherapy-refractory disease, defined as one or more of the following:
- •No response to first-line therapy (primary refractory disease)
- •No response to second or greater lines of therapy OR
- •Refractory after autologous stem cell transplant (ASCT)
- •At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).
- •Individuals must have received adequate prior therapy, including at a minimum:
- •Anti-CD20 monoclonal antibody
- •An anthracycline-containing chemotherapy regimen
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate renal, hepatic, pulmonary, and cardiac function
排除标准
- •Known CD19 negative or CD20 negative tumor
- •History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
- •Prior CAR therapy or other genetically modified T-cell therapy
- •Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
- •Prior CD19 targeted therapy
- •Clinically significant infection or cardiopulmonary disease
- •Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
- •History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
- •History of autoimmune disease
- •History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab 375 mg/m^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m^2 over 30 minutes and cyclophosphamide 500 mg/m^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.
干预措施: Axicabtagene Ciloleucel (Biological)
Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab 375 mg/m^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m^2 over 30 minutes and cyclophosphamide 500 mg/m^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.
干预措施: Rituximab (Drug)
Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab 375 mg/m^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m^2 over 30 minutes and cyclophosphamide 500 mg/m^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.
干预措施: Fludarabine (Drug)
Axicabtagene Ciloleucel and Rituximab Combination
Participants will receive rituximab 375 mg/m^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m^2 over 30 minutes and cyclophosphamide 500 mg/m^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators
时间窗: First infusion date up to maximum duration of 32.7 months
CR rate is defined as the incidence of a CR per the IWG Lugano Classification as determined by study investigators. CR rate: percentage of participants with CR \[complete metabolic response (CMR); complete radiological response (CRR)\]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology. 95% confidence interval (CI) was calculated by Clopper-Pearson method.
次要结局
- Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value(First infusion date up to maximum duration of 27 months)
- Peak Level of Anti-CD19 CAR T Cells in Blood(Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24)
- Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)(First infusion date up to maximum duration of 27 months)
- Duration of Response (DOR) Per the IWG Lugano Classification as Determined by Study Investigators(From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 32.7 months))
- Overall Survival (OS)(First infusion date up to death regardless of cause (up to approximately 32.7 months))
- Area Under the Curve of CAR T Cells From Day 0 to Day 28 (AUC0-28)(Baseline (Day 0), post-infusion on Days 7, 14, 21, and 28)
- Time to Peak Level of Anti-CD19 CAR T Cells in Blood(Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24)
- Objective Response Rate (ORR) Per the IWG Lugano Classification as Determined by Study Investigators(First infusion date up to maximum duration of 32.7 months)
- Progression-Free Survival (PFS) Per the IWG Lugano Classification as Determined by Study Investigators(First infusion date up to disease progression or death regardless of cause (up to approximately 32.7 months))
- Level of Anti-CD19 CAR T Cells in Blood by Visit(Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24)