NCT04014894Unknown1 期
Safety and Efficiency Study of ET019003-T Cells in Relapsed/Refractory CD19+ B-Cell Leukemia and Lymphoma
Wuhan Union Hospital, China1 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2019年6月12日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-related Adverse Events
研究概览
简要总结
This is a single center, open-label, 3+3 dose escalation, phase 1 study to evaluate the efficacy and safety of ET019003-T cells therapy for patients with relapsed/refractory CD19+ acute lymphoblastic leukemia and lymphoma.
详细描述
ET019003-T cells is a human anti-CD19 CAR-T cells by fusing the anti-CD19 antibody Fab domain with the transmembrane and intracellular domains from the γδTCR, which can avoid mispairing with the T cell's endogenous αβTCR chains. Meanwhile, an independent ET190L1-CSR(Chimeric Signaling Receptor) is added to ET019003-T cells in trans, which can bind CD19 to activate a novel costimulatory domain to further promote T cell proliferation and persistence.
The trial is conducted to explore the safety and efficacy of ET019003-T cells in CD19+ Leukemia and Lymphoma.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
- •Male or female, aged 18 to 75 years (including 18 and 75 years old).
- •Pathologically confirmed CD19+ B-cell malignancies, and patients met the following criteria for refractory or relapsed B-cell malignancies.
- •A. Refractory/relapsed B-cell lymphoblastic leukemia (meeting one of the following) i. Recurrence within 6 months after first remission. ii. Primary refractory disease which cannot achieve complete remission (CR) after 2 cycles of standardized chemotherapy regimen.
- •iii. Failure to achieve CR or relapse after one line or multiple lines of salvage chemotherapy.
- •iv. Not suitable for hematopoietic stem cell transplantation (HSCT), or abandon HSCT due to various restrictions, or relapse after HSCT.
- •B. Refractory/relapsed B-cell lymphoma (Meeting 1 of the first 3 items plus item 4) i. Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
- •ii. Achieved CR after standard chemotherapy, but relapsed within 6 months. iii. Two or more relapses after CR. iv. Subjects must have received adequate treatment in the past, including anti-CD20 monoclonal antibody and combination chemotherapy with anthracyclines.
- •Having a measurable or evaluable lesion:
- •A. Patients with lymphoma require a single lesion≥15mm or 2 or more lesions≥10mm.
- •B. Patients with leukemia require persistent positive or positive relapse of bone marrow MRD.
- •Patient's main organs functioning well:
- •A. Liver function: ALT/AST ≤ 3 times the upper limit of normal (ULN) and total bilirubin≤2 times ULN.
- •B. Renal function: Creatinine < 220μmol/L. C. Pulmonary function: Indoor oxygen saturation≥95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 50%.
- •≥ 2 weeks since prior therapy at the time of enrollment, and the toxicity related to previous treatments returned to < grade 1 (except for low grade toxicity such as alopecia).
- •ECOG score≤
- •Estimated survival time≥3 months.
排除标准
- •Women who are pregnant or breastfeeding.
- •Women of child-bearing potential and all male participants can't use effective methods of contraception for at least 12 months following infusion.
- •Patients fail to collect enough PBMC.
- •Patients with other uncontrolled diseases, such as active infections.
- •Active hepatitis B or active hepatitis C.
- •Known HIV positive patients.
- •Patients with active autoimmune diseases requiring systemic immunosuppressive therapy.
- •Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within 3 years.
- •Patients with severe mental disorder or disorders of consciousness.
- •Patients who need immediate treatment to control tumor progression or relieve tumor burden.
- •Patients participated in other clinical treatments within 6 weeks.
- •Patients with drug addiction.
- •Patients with poor treatment compliance.
研究组 & 干预措施
ET019003-T Cells
Experimental
The trial will enroll 9 patients with leukemia and 9 patients with lymphoma. Each disease has 3 dose-levels.
干预措施: ET019003-T Cells (Drug)
结局指标
主要结局
Incidence of Treatment-related Adverse Events
时间窗: 3 years
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).
次要结局
- Overall Remission Rate(ORR) of ET019003-T cells in Leukemia and Lymphoma(3 years)
- Progress-free survival(PFS) of ET019003-T cells in Leukemia and Lymphoma(3 years)
- Overall survival(OS) of ET019003-T cells in Leukemia and Lymphoma(3 years)
- duration of Response(DOR) of ET019003-T cells in Leukemia and Lymphoma(3 years)
- Rate of ET019003-T cells in bone marrow cells and peripheral blood cells(3 years)
- Quantity of ET019003-T CAR copies in bone marrow cells and peripheral blood cells(3 years)
研究者
MEI HENG
Principal Investigator
Wuhan Union Hospital, China
研究点 (1)
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