The Safety and Efficacy of CD19 & CD20 Bispecific CAR T Cells in Treating Relapsed / Refractory B Cell Hematological Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-related Adverse Events
研究概览
简要总结
This study is a multi-center, open, prospective single-arm clinical study of patients with relapsed / refractory B cell hematological tumors to evaluate the safety and efficacy of CD19 & CD20 bispecific CAR-T cells in relapsed / refractory B cell hematological tumors while collecting pharmacokinetics and pharmacodynamics indicators of CAR-T cells.
详细描述
Since 2010, CAR-T ( chimeric antigen receptor T cell) therapy has shown good results in tumor treatment and has achieved positive clinical therapeutic effects in hematological tumors. The structure of the dual-target CAR-T of CD19 & CD20 is designed with a 4-1BB costimulatory domain and an antigenic recognition region with a tandem structural sequence to recognize CD20 or CD19 by a single structure. CD19 & CD20 bispecific CAR-T cells can identify CD 19 or CD 20 with the advantage that the single target CAR-T does not have, reducing the possibility of target loss. The structure has been optimized to enhance the safety to treat B cell-derived hematological tumors (at least CD19 positive or CD20 positive).
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
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully understand and voluntarily sign the informed consent form, and be willing and able to comply with the visit, treatment protocol, laboratory tests, and other study requirements specified in the flow sheet;
- •CD 19 + / CD 20 + B cell hematological tumor was confirmed by pathological and histological examination, and the patient met the following criteria for relapsed or refractory B cell hematological tumor:
- •Refractory / relapsed B lymphocytic leukemia (1 of the following 4 items can be met):
- •i . Recurrence within 6 months of first remission; ii. Primary refractory without complete remission after 2 cycles of standard chemotherapy regimen; iii. No complete remission or recurrence after first-line or multiline salvage chemotherapy; iv. Not eligible for HSCT conditions, abandonment of HSCT, or relapse after HSCT due to conditional limitations.
- •Refractory / relapsed B-cell lymphoma (meet the following item 1 of the first 4 items plus item 5):
- •i . After four courses of chemotherapy with a standard regimen, tumor shrinkage was less than 50% or disease progression; ii . CR after standard regimen chemotherapy, but relapsed within 6 months; iii.2 or more recurrences after CR; iv . Not suitable for hematopoietic stem cell transplantation, or abandoning HSCT due to conditional restrictions or relapse after hematopoietic stem cell transplantation; v . Subject must have received prior adequate treatment, including at least: a monoclonal antibody against CD 20 and combination chemotherapy containing an anthracycline drug agent.
- •B-cell hematological tumors include the following 3 categories:
- •B-cell acute lymphoblastic leukemia (B-ALL);
- •Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL);
- •Invasive B-cell lymphoma (DLBCL, BL, and MCL);
- •With measurable or evaluable lesions: Lymphoma patients require a single lesion 15mm or 2 or more lesions 10mm; patients with leukemia require persistent positive or positive recurrence of bone marrow MRD.
- •Subjects with the Eastern Cooperative Oncology Group (ECOG) fitness scores of 0 to
- •The results of FCM or immunohistochemical detection of tumor antigen (CD 19 / CD 20) were positive.
- •The estimated survival period is more than 3 months starting from the signing of the informed consent form.
排除标准
- •Appearance of one of the following cardiac criteria: atrial fibrillation; myocardial infarction in the last 12 months; prolonged QT syndrome or secondary QT extension, as judged by the investigator. Echocardiography LVSF <30% or LVEF <50%; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV (confirmed by echocardiography within 12 months of treatment).
- •Active GVHD.
- •History of severe pulmonary function impairment disease.
- •Other malignant tumors in the advanced stage.
- •Severe infection or persistent infection that cannot be effectively controlled.
- •Combined with severe autoimmune disease or innate immune deficiency.
- •Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA 500 IU / ml and abnormal liver function] or hepatitis C antibody [HCV-Ab] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function).
- •Human immunodeficiency virus (HIV) infection or syphilis infection.
- •History of severe allergies to biological products (including antibiotics).
- •There are central nervous system disorders, such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, etc..
- •Female patients are in pregnancy and lactation, or have a pregnancy plan within 12 months.
- •situations where the investigator may increase the risk or interfere with the test results.
研究组 & 干预措施
Effective of CD19&CD20 bispecific CAR-T cells
The infusion dose range of cells in this trial is recommended: 2 to 6 10^6 And CAR-T cells / kg.
干预措施: CD19&CD20 bispecific CAR-T cells (Drug)
结局指标
主要结局
Incidence of Treatment-related Adverse Events
时间窗: within 3 years after infusion
Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Partial response rate (PR) of administering CD19&CD20 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors
时间窗: within 3 year after infusion
PR will be assessed from CAR-T cell infusion to death or last follow-up.
Overall response rate (ORR) of administering CD19&CD20 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors
时间窗: within 3 years after infusion
Disease overall response rate (ORR) will be assessed from CAR-T cell infusion to death or last follow-up (censored).
Complete response rate (CR) of administering CD19&CD20 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors
时间窗: within 3 years after infusion
CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).
次要结局
- Overall survival (OS) of administering CD19&CD20 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors(within 3 years after infusion)
- Progress-free survival (PFS) of administering CD19&CD20 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors(within 3 years after infusion)
- Event-free survival (EFS) of administering CD19&CD20 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors(within 3 years after infusion)
研究者
MEI HENG
: Proferssor, Cheif Doctor
Wuhan Union Hospital, China