A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR20A in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 5
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR20A in adult subjects with r/r B-cell NHL or r/r CLL/SLL.
详细描述
This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate safety, tolerability, clinical activity, and find an appropriate dose to optimize safety and efficacy of PBCAR20A in subjects with relapsed/refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Before initiating PBCAR20A, therapy, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive a single intravenous (IV) infusion of PBCAR20A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR20A will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- •Criteria for NHL:
- •Requirement for urgent therapy due to mass effects such as bowel obstruction, spinal cord, or blood vessel compression.
- •Active central nervous system (CNS) disease. A negative computed tomography (CT)/magnetic resonance imaging (MRI) is required at Screening if the study participant has a history of CNS lymphoma.
- •Criteria for NHL and CLL/SLL:
- •Active CNS disease. A negative lumbar puncture is required at Screening if the study participant has a history of CNS disease.
- •Previous malignancy, besides the malignancies of inclusion (B-cell NHL or CLL/SLL), that in the investigator's opinion, has a high risk of relapse in the next 2 years.
- •Active uncontrolled fungal, bacterial, viral, protozoal, or other infection.
- •Any form of primary immunodeficiency.
- •History of human immunodeficiency virus (HIV) infection.
- •Active hepatitis B or C.
- •Uncontrolled cardiovascular disease.
- •Hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
- •Presence of a CNS disorder that renders ineligible for treatment.
- •History of a genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman Diamond syndrome, or any other known bone marrow failure syndrome.
- •Received ASCT within 45 days of Screening if the study participant has met the rest of the count requirements.
- •Must not have received systemic corticosteroid therapy for at least 7 days prior to initiating lymphodepletion chemotherapy.
- •Received a live vaccine within 4 weeks before Screening.
- •Radiotherapy within 4 weeks determined on a case-by-case basis.
- •Presence of a pleural/peritoneal/pericardial catheter.
- •Current use of any anticoagulant or antiplatelet therapy.
研究组 & 干预措施
Dose Level 3 of PBCAR20A CAR T cells
480 x 10^6 CAR T cells (flat dose)
干预措施: Fludarabine (Drug)
Dose Level 3 of PBCAR20A CAR T cells
480 x 10^6 CAR T cells (flat dose)
干预措施: Cyclophosphamide (Drug)
Dose Level 1 of PBCAR20A CAR T cells
1 x 10^6 chimeric antigen receptor (CAR) T cells per kg body weight.
In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
Route of Administration: Intravenous infusion (IV)
Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: PBCAR20A (Genetic)
Dose Level 1 of PBCAR20A CAR T cells
1 x 10^6 chimeric antigen receptor (CAR) T cells per kg body weight.
In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
Route of Administration: Intravenous infusion (IV)
Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: Fludarabine (Drug)
Dose Level 1 of PBCAR20A CAR T cells
1 x 10^6 chimeric antigen receptor (CAR) T cells per kg body weight.
In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
Route of Administration: Intravenous infusion (IV)
Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
干预措施: Cyclophosphamide (Drug)
Dose Level 2 of PBCAR20A CAR T cells
240 x 10^6 CAR T cells (flat dose)
干预措施: PBCAR20A (Genetic)
Dose Level 2 of PBCAR20A CAR T cells
240 x 10^6 CAR T cells (flat dose)
干预措施: Fludarabine (Drug)
Dose Level 2 of PBCAR20A CAR T cells
240 x 10^6 CAR T cells (flat dose)
干预措施: Cyclophosphamide (Drug)
Dose Level 3 of PBCAR20A CAR T cells
480 x 10^6 CAR T cells (flat dose)
干预措施: PBCAR20A (Genetic)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Day 1 to Day 28
The maximum tolerated dose (MTD) is the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.
Number of Participants With Dose-Limiting Toxicities
时间窗: 1 year
Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.
次要结局
- Objective Response Rate(1 year)
- Progression-free Survival (PFS)(1 year)