Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 30
- 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, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of BCMA-PD1-CART cells therapy for patients with relapsed/refractory Multiple Myeloma.
详细描述
Previous studies have found that multiple myeloma cells express PD-L1 at a high level. Therefore, the combination of anti-PD-1 or PD-L1 antibodies with CART therapy may further improve the clinical efficacy of CART cell for multiple myeloma.
The investigators screened PD-1 mutant that have high affinity bind with the PD-L1 ligand, and the affinity of the prepared mutant PD-1 Fc fusion protein to bind to PD-L1 reached clinical anti-PD-L1 antibody levels. The investigators prepared BCMA CART cells which secretes the mutant PD-1Fc fusion protein, and the prepared CART cell culture supernatant can well block the binding of PD-L1 to PD-1. Preclinical studies have shown that BCMA CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect on PD-L1 positive multiple myeloma tumor cells to BCMA CART cells which does not express PD-1 fusion protein.
The trial was conducted to explore the safety and efficacy of BCMA-PD1-CART cells in Relapsed/Refractory 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
- 14 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 14 to 80 years (including 14 and 80 years old).
- •The diagnosis was Refractory/relapsed multiple myeloma.(Meeting 1 of the follow 3 items)
- •A.Primary treatment patients with no effect after first and second line treatment.
- •B.Patients who relapsed after complete remission and failed to respond to two kind of therapy.
- •C.the predicted survival is more than three months.
- •Flow cytometry or immunohistochemistry showed BCMA positive in tumor cells.
- •Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
- •No serious concomitant disease and major organ function is not serious abnormal.
- •No serious concomitant disease and major organ function is not serious abnormal.
- •the test meets the following indicators:
- •A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L.
- •B.WBC≥2.5×109/L.
- •C.PT/INR < 1.7 or PT was extended by less than 4 seconds.
排除标准
- •Women who are pregnant or breastfeeding.
- •Transduced positive T lymphocytes < 5% or amplified against CD3/CD28 stimulation < 5 times.
- •Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection.
- •Patients who are using steroid drugs throughout the body currently.
- •Patients who have received any gene therapy in the past.
- •Patients who are allergy to immunotherapy and related drugs.
- •Patients with heavy heart disease or poorly controlled high blood pressure.
- •Patients who received chemotherapy or radiation 4 weeks before the study began.
- •Patients who are participating in other clinical trials.
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 BCMA-PD1-CART cells in Lymphoma(3 years)
- Overall survival(OS) of BCMA-PD1-CART cells in Lymphoma(3 years)
- Progress-free survival(PFS) of BCMA-PD1-CART cells in Lymphoma(3 years)
- Rate of BCMA-PD1-CARTcells in peripheral blood cells(3 years)
- Quantity of BCMA-PD1-CART cells copies in peripheral blood cells.(3 years)
研究者
Quanshun Wang
Chief of Hematology Department of Hainan Hospital of PLA General Hospital; Vice Chief of Hematology Department of PLA General Hospital
Chinese PLA General Hospital