An Open-label Clinical Study on the Efficacy and Safety of CD7-specific CAR-T Cell Injection in the Treatment of CD7-positive Relapsed/Refractory Hematologic 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
- Overall response rate (ORR) of administering CD7-specific CAR-T Cells In the treatment of relapsed/refractory hematologic tumors
研究概览
简要总结
This study is a single-center, open, prospective single-arm clinical study of patients with CD7 postive relapsed / refractoryhematological tumors to evaluate the safety and efficacy of CD7-specific CAR-T cells in relapsed / refractory hematological tumors while collecting pharmacokinetics and pharmacodynamics indicators of CAR-T cells.
详细描述
In order to study CD7-targeting CAR-T cell therapy, we constructed a lentiviral CAR structure. The CD7-targeting fragment was cloned into a second-generation CAR structural backbone with 4-1BB and CD3E. Since endogenous CD7 in T cells causes CD7-targeting CAR-T cells to kill each other, we used a natural selection method to prepare CD7-targeting CAR (CD7-CART) T cells that do not express the CD7 protein (CD7-).
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
- 3 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with a diagnosis of relapsed/refractory hematologic malignancies that meet any of the following criteria:
- •Recurrence: peripheral blood or bone marrow blasts (proportion>5%) after achieving complete remission after previous standard treatment regimens, or extramedullary disease, including:
- •i) Early recurrence within 12 months; ii) Late recurrence of 12 months or more with no remission after one course of standard induction chemotherapy; iii) Relapse after autologous or allogeneic hematopoietic stem cell transplantation.
- •Refractory: complete remission is not achieved after at least two courses of standard induction therapy, or complete remission is not achieved after first-line or above salvage therapy
- •At the time of enrollment screening, bone marrow flow cytometry detected tumor cells as CD7 expression and/or pathological immunohistochemistry of extramedullary lesions was confirmed that tumor cells expressed CD
- •If tumor cells are detected in peripheral blood during enrollment screening, the immunophenotype of tumor cell surface at the time of flow cytometry detection should be CD4 and CD8 negative. If the surface immunophenotype of peripheral blood tumor cells is not CD4 and CD8 negative, the condition of ≤1% proportion of peripheral blood tumor cells must be met.
- •Subjects with the Eastern Cooperative Oncology Group (ECOG) fitness scores of 0 to
- •Expected survival over 3 months;
- •Liver, kidney and cardiopulmonary functions meet the following requirements:
- •Serum creatinine ≤ 1.5× ULN；
- •Left ventricular ejection fraction (LVEF) ≥50%;
- •Baseline peripheral oxygen saturation > 90%;
- •Total bilirubin ≤ 1.5×ULN; ALT and AST ≤2.5×ULN.
- •Patient or his or her legal guardian voluntarily participates in and signs an 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).
- •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
Fludarabine + Cyclophosphamide +CD7-specific CAR-T Cells
Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (300 mg/kg) on day -5, -4, and -3, followed by the infusion of CD7-specific CAR-T Cells with the dose of 1-3×10^6/kg.
干预措施: Fludarabine + Cyclophosphamide + CD7-specific CAR-T Cells (Drug)
结局指标
主要结局
Overall response rate (ORR) of administering CD7-specific CAR-T Cells In the treatment of relapsed/refractory 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).
Incidence of Treatment-related Adverse Events
时间窗: Within 3 month after CD19&CD20 CAR-T 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).
次要结局
- In vivo expansion and survival of CD7-specific CAR-T Cells in relapsed/refractory hematological malignancies(within 3 years after infusion)
研究者
MEI HENG
: Proferssor, Cheif Doctor
Wuhan Union Hospital, China