NCT04662099招募中1 期
Safety and Efficacy of the Bispecific CAR T Therapy Targeting CS1 and BCMA in Patients With Relapsed/ Refractory Multiple Myeloma: a Single-center, Open-label, Single-arm Clinical Study
Wuhan Union Hospital, China1 个研究点 分布在 1 个国家目标入组 24 人开始时间: 2020年3月25日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 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, single-arm study to evaluate the safety and efficacy of the bispecific CAR T cells targeting CS1 and BCMA in patients with relapsed or refractory multiple myeloma.
详细描述
- Multiple myeloma(MM) is one of the most common hematological malignancies with substantial morbidity and mortality.
- In recent years, several new therapies have prolonged survival of patients with MM, but it is still an incurable malignancy of plasma cells.
- B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells and a small subset of B cells. This specific expression pattern makes BCMA an ideal target antigen for immunotherapies in MM.
- BCMA-targeted chimeric antigen receptor (CAR) T cells have exhibited significant efficacy in MM, but relapse due to single-target escape or poor in vivo persistence has been reported.
- Dual-targets or sequential infusion have been proposed to reduce relapse and improve outcomes post BCMA-specific CAR T therapies.
- CS1 is expressed on pro-B cells and plasma cells especially malignant ones and some evidence suggests it plays a role in stromal cell interaction in the BM tumour microenvironment.
- We have constructed a bispecific CAR containing anti-CS1 single chain variable region (scFv) and an anti-BCMA scFv in 4-1BB-containing second-generation formats.
- The bispecific CAR T cells have exhibited potent cytotoxicity in various BCMA+ or/and CS1+ MM cells and can effectively eradicate MM cells in xenograft mice models.
- This study aims to evaluate prelimary safety and efficacy of the CS1&BCMA CAR T cells in patients with relapsed or refractory MM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Each potential subject must meet all of the following criteria to be enrolled in the study:
- •Aged 18-78 years old, males or females.
- •Relapsed or refractory multiple myeloma according to IMWG diagnostic criteria.
- •Received at least 2 prior lines of treatment for multiple myeloma, including a proteasome inhibitor and an immunomodulatory drug.
- •Detectable MM cells in bone marrow by conventional morphologic methods or flow cytometry, and positive expression of CS1 or BCMA on MM cells as confirmed by immunohistochemistry or flow cytometry.
- •Measurable diseases at screening as defined by any of the following:
- •Serum M-protein level ≥1.0g/dL;
- •Urine M-protein level ≥200mg/24 hours;
- •Serum immunoglobulin free light chain(FLC) ≥10 mg/dL provided abnormal FLC ratio.
- •Recovery to grade 1 or baseline of toxicities due to prior treatment, excluding hematologic toxicities and toxicity of no clinical significance, like alopecia.
- •ECOG Performance Status 0 ~ 2 (ECOG status of larger than 2 points caused by MM osteolytic destruction is accepted).
- •Good organ function at screening as defined by any of the following:
- •AST and ALT ≤ 2.5×upper limit of normal (ULN);
- •Total bilirubin≤ 2.0×ULN;
- •Creatinine clearance ≥30 mL/min/1.73m2;
- •Ejection fraction of heart ≥50%, and no clinically significant abnormal ECG findings.
- •Clinical laboratory values meeting the following criteria at screening:
- •Absolute Neutrophil Count(ANC) ≥1.0×10^9/L;
- •Platelets ≥30×10^9/L;
- •Absolute Lymphocyte Count ≥1.0×10^8/L;
- •Hemoglobin(Hb) ≥6.0g/dL.
- •Women of childbearing potential must have a negative pregnancy test at screening.
- •Patients with extramedullary lesions were eligible.
- •Patients who received prior allogeneic or autologous stem cell transplantation at least three months before screening were eligible.
- •Sign the informed consent voluntarily.
排除标准
- •Any potential subject who meets any of the following criteria will be excluded from participating in the study:
- •Evidence of serious viral, bacterial, or uncontrolled systemic fungal infection.
- •Seropositive for human immunodeficiency virus (HIV) antibody.
- •Seronegative for hepatitis B antigen or a known history of hepatitis B.
- •Hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive) or a known history of hepatitis C.
- •Systemic corticosteroid therapy of greater than 5 mg/day of prednisone or equivalent dose within 2 weeks prior to apheresis.
- •Active autoimmune disease or a history of autoimmune disease within 3 years.
- •The following cardiac conditions: Myocardial infarction or coronary artery bypass graft ≤6 months prior to enrollment; History of clinically significant ventricular arrhythmia or unexplained; New York Heart Association stage III or IV congestive heart failure.
- •A history of epilepsy or other central nervous system diseases or altered mental status.
- •Known life-threatening allergies, hypersensitivity, or intolerance to CAR-T cells or relevant lymphodepleting regimens (cyclophosphamide and fludarabine).
- •Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within one year after receiving study treatment.
- •Any uncontrolled diseases, other than multiple myeloma, that may lead to abnormal death.
- •Being participating in other intervention studies.
- •Other cases excluded by the Investigators.
结局指标
主要结局
Incidence of Treatment-related Adverse Events
时间窗: within 2 years after infusion
Therapy-related adverse events 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
- Overall response rate(ORR) and complete response rate(CRR) of administering T cells Expressing a bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma(2 years after infusion)
- Overall survival(OS), duration of Response(DOR), progress-free survival(PFS) of administering T cells Expressing a bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma(2 years after infusion)
研究者
MEI HENG
Proferssor, Cheif Doctor
Wuhan Union Hospital, China
研究点 (1)
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