A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-12)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 7
- 主要终点
- Complete Response (CR) Rate Per the 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 participants with high-risk large B-cell lymphoma.
After the end of KTE-C19-112 (ZUMA-12), participants who received an infusion of axicabtagene ciloleucel will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968.
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
- •High-grade large B-cell lymphoma
- •Individuals must have a positive interim positron emission tomography (PET) (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
- •No evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Absolute neutrophil count ≥ 1000/μL
- •Platelet count ≥ 75,000/μL
- •Absolute lymphocyte count ≥ 100/μL
- •Adequate renal, hepatic, pulmonary, and cardiac function defined as:
- •Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
- •Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal (ULN)
- •Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome
- •Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
- •No clinically significant pleural effusion
- •Baseline oxygen saturation > 92% on room air
排除标准
- •History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
- •History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma
- •History of autologous or allogeneic stem cell transplant
- •Prior CD19-targeted therapy
- •Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
- •Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
- •History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
- •Presence of any indwelling line or drain dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
- •Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma
- •History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- •History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
- •History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
- •History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Axicabtagene Ciloleucel
Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV conditioning 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. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered.
Participants who achieve partial response or complete response and subsequently experience disease progression will have an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants will receive the same axicabtagene ciloleucel regimen as the original target dose anytime during the study.
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 conditioning 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. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered.
Participants who achieve partial response or complete response and subsequently experience disease progression will have an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants will receive the same axicabtagene ciloleucel regimen as the original target dose anytime during the study.
干预措施: Fludarabine (Drug)
Axicabtagene Ciloleucel
Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV conditioning 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. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10^8 anti-CD19 CAR T cells will be administered.
Participants who achieve partial response or complete response and subsequently experience disease progression will have an option to receive second course of conditioning chemotherapy therapy and axicabtagene ciloleucel. Participants will receive the same axicabtagene ciloleucel regimen as the original target dose anytime during the study.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
时间窗: Up to 4 years
CR Rate is the 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.
次要结局
- Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators(Up to 4 years)
- Duration of Response (DOR) Per the Lugano Classification(Up to 4 years)
- Event-Free Survival (EFS)(Up to 4 years)
- Progression-Free Survival (PFS)(Up to 4 years)
- Overall Survival (OS)(Up to 4 years)
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE)(Up to 2 years)
- Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value(Up to 2 years)
- Percentage of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value(Up to 2 years)
- Relapse With Central Nervous System (CNS) Disease(Up to 4 years)
- Pharmacokinetics: Peak Level of Anti-CD19 CAR T Cells in Blood(Up to Month 24)
- Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8(Up to Week 4)
- Peak Serum Level of C-Reactive Protein (CRP)(Up to Week 4)
- Peak Serum Level of Ferritin(Up to Week 4)
- Time to Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8, CRP, and Ferritin(Up to Week 4)