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临床试验/NCT03778346
NCT03778346Unknown1 期

Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells

The Sixth Affiliated Hospital of Wenzhou Medical University3 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2018年11月15日最近更新:
适应症

试验速览

阶段
1 期
发起方
入组人数
30
试验地点
3
主要终点
Adverse events that are related to treatment

研究概览

简要总结

According to the high expression of tumor cell-associated antigen CD138, integrin β7, CS1, CD38 and BCMA in patients with refractory/recurrent multiple myeloma, the fourth generation of CAR-T cells(simultaneously expressing IL7 and CCL19) with 10 different dual target combinations are used to minimize the tumor burden in the patient individually and precisely and improve the immunosuppressive microenvironment of the tumor , thereby effectively treating refractory/recurrent multiple myeloma .

详细描述

Multiple myeloma(MM) is one of the most common malignant diseases in the blood system.There is still no cure for the disease which only control the development of the disease in various ways including proteasome inhibitors and immune regulator and hematopoietic stem cell transplantation . Combined with the advantages of multiple therapies, chimeric antigen receptor T cells (CAR-T) have gradually becoming one of the strongest and most powerful weapons against multiple myeloma.The basic principle is to use the patient's own immune cells to clear cancer cells.

MM is genetically and phenotypically heterogeneous,Antigen escape and relapse after CAR-T treatment is a global problem, so the effective treatment of refractory/relapsing multiple myeloma with CAR-T cells usually requires targeting multiple antigens. The investigators use Integrin β7(a large family of molecules that are central regulators in multicellular biology and orchestrating cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function), BCMA(highly expressed on malignant MM plasma cells and providing a substantial antiapoptotic signal making it an encouraging target for BCMA-directed immunotherapy),CS1(encoded by the SLAMF7 gene,a robust marker of normal plasma cells and malignant plasma),CD38(encoded by the CD38 gene and functioning in cell adhesion, signal transduction and calcium signaling) and CD138(known as syndecan 1, a surface protein expressed on most healthy and malignant plasma cells as an adhesion protein, binding collagen and fibronectin molecules located in the extracellular matrix. ) as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells ,thereby effectively treating refractory/recurrent multiple myeloma .

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 80 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Patients who meet the requirements voluntarily participate in the study and sign the Informed Consent Form.
  • Age is 18 to 80 years old, gender is not limited.
  • Patients with relapsed or refractory myeloma who meet the following criteria for multiple myeloma diagnostic criteria defined by the IMWG (2017): Subjects have received adequate prior treatment of at least 2 regimens; during the most recent treatment or after treatment , the disease progresses or recurs.
  • The Eastern Cancer Cooperative Group (ECOG) scores 0 to 2 (the tumor causes bone pain).
  • The expected survival period is more than 12 weeks.
  • No other malignant tumors, severe autoimmune diseases or congenital immunodeficiency, serious progressive infection, cranial nerve disorder or mental illness.

排除标准

  • Pregnant or lactating women.
  • Patients with uncontrollable active infections.
  • Patients with systemic steroids; recent or current use of inhaled steroids is not excluded.
  • Previously involved CAR-T cell therapies produced any uncontrolled disease.

结局指标

主要结局

Adverse events that are related to treatment

时间窗: 2 years

Safety and tolerability measured by occurrence of study related adverse effects defined by NCI-CTCAE v4.03

次要结局

  • 3 year progression free survival (PFS)(3 yaers)
  • 2 year overall survival(OS)(2 yaers)

研究者

发起方
The Sixth Affiliated Hospital of Wenzhou Medical University
申办方类型
Other
责任方
Sponsor

研究点 (3)

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