A Phase 1b/2 Study of a Anti-CD19/CD20 Bispecific CAR-T Therapy (C-CAR039/Prizloncabtagene Autoleucel) in Patients With Relapsed/Refractory Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 112
- 试验地点
- 15
- 主要终点
- Phase 1b: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a multicenter, single arm, open-label study. The purpose of the study is to evaluate safety of Prizloncabtagene Autoleucel (Prizlon-cel) and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of Prizlon-cel (Phase 2) in patients with relapsed or refractory large b-cell lymphoma (LBCL).
详细描述
The purpose of the study is to evaluate the safety and efficacy of Prizlon-cel. It includes two phases, Phase 1b and Phase 2. In Phase 1b study, RP2D will be determined. The selected dose will be further evaluated in the Phase 2 study. The study includes the following sequential procedures: Screening, Apheresis and CAR-T manufacturing, Baseline, Lymphodepletion, CAR-T infusion, DLT period (Phase 1b) and Follow-up Visit. Subjects will be followed for at least 2 years after Prizlon-cel infusion, with up to 15 years long-term follow-up on a separate 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
- •≥ 18 years of age
- •Histologically confirmed CD19 or CD20 positive B-cell non-Hodgkin lymphoma, including the following neoplasms as defined by the 2016 WHO classification of lymphoid neoplasms:
- •Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS)
- •Primary mediastinal large B-cell lymphoma (PMBCL)
- •Transformed follicular lymphoma (tFL)
- •High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH)
- •High-grade B-cell lymphoma, NOS (HGBL, NOS)
- •Follicular lymphoma grade 3B (FL3B)
- •Relapsed or refractory disease after ≥ 2 lines of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
- •At least one measurable lesion per the Lugano 2014 Classification
- •Adequate organ and marrow function
排除标准
- •Prior allogeneic hematopoietic stem cell transplantation (HSCT) at anytime, or ASCT within 12 weeks prior to apheresis
- •Suspected or confirmed central nervous system involvement
- •Stroke or convulsion history within 6 months of signing informed consent form (ICF)
- •Autoimmune disease, immunodeficiency or diseases requiring immunosuppressants treatment
- •Uncontrolled active infection
- •Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with detectable hepatitis B virus (HBV) DNA in peripheral blood; positive hepatitis C virus (HCV) antibody with positive HCV RNA in peripheral blood; positive human immunodeficiency virus (HIV) antibody; positive syphilis test
- •Severe heart, liver, renal or metabolism disease
- •Inadequate wash-out time for previous anti-tumor treatments prior to apheresis
- •Prior CAR-T therapy
研究组 & 干预措施
Prizloncabtagene Autoleucel
Prizlon-cel will be intravenously administered as a single infusion after lymphodepletion.
干预措施: Prizloncabtagene autoleucel (Biological)
结局指标
主要结局
Phase 1b: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 90 days after C-CAR039 infusion
Incidence and severity of TEAEs , including dose limiting toxicities (DLTs)
Phase 1b: Recommended Phase 2 Dose (R2PD)
时间窗: Up to 3 months after C-CAR039 infusion
Based on DLTs rates and overall safety profile
Phase 2: Overall Response Rate (ORR) at 3 months
时间窗: Up to 3 months after C-CAR039 infusion
Best response rate at 3 months after C-CAR039 infusion, including partial response (PR) and complete response (CR)
次要结局
- Phase 1b: Incidence and Severity of Adverse Events (AEs)(Up to 2 years after C-CAR039 infusion)
- Time to response (TTR)(Up to 2 years after C-CAR039 infusion)
- Time to reach the maximal plasma concentration (Tmax)(Up to 2 years after C-CAR039 infusion)
- Phase 1b: ORR at 3 months(Up to 3 months after C-CAR039 infusion)
- Phase 2: Incidence and Severity of Adverse Events (AEs)(Up to 2 years after C-CAR039 infusion)
- ORR(Up to 2 years after C-CAR039 infusion)
- ORR at 6 months(Up to 6 months after C-CAR039 infusion)
- Duration of response (DOR)(Up to 2 years after C-CAR039 infusion)
- Overall survival (OS)(Up to 2 years after C-CAR039 infusion)
- Progression-free survival (PFS)(Up to 2 years after C-CAR039 infusion)
- Maximal plasma concentration (Cmax)(Up to 2 years after C-CAR039 infusion)
- Area under the curve within 28 days (AUC0-28d)(Up to 28 days after C-CAR039 infusion)
- Time of last measurable observed concentration (Tlast)(Up to 2 years after C-CAR039 infusion)
- The B cell percentage changes and CD19/CD20 expression changes in blood(Up to 2 years after C-CAR039 infusion)
- Anti-drug (C-CAR039) antibody(Up to 2 years after C-CAR039 infusion)