NCT05016778进行中（未招募）早期 1 期
A Single Arm, Open Label Clinical Study of CAR-T Cells Targeting GPRC5D in the Treatment of Relapsed / Refractory Multiple Myeloma(POLARIS)
Zhejiang University1 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2021年6月8日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- AE and SAE
研究概览
简要总结
This is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability, cellular kinetics and initial efficacy of CAR-T cell therapy targeting GPRC5D in multiple myeloma subjects who have failed the standard treatments.
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
- •The subject can understand and have the ability to sign an informed consent form;
- •Male or female subjects, aged 18-75 years;
- •The expected survival period is not less than 12 weeks;
- •ECOG score ≤ 2 ;
- •Diagnosed as multiple myeloma according to the IMWG standard in 2018;
- •The expression of GPRC5D in bone marrow plasma cells is more than 20%, or it is positive in tumor tissue by immunohistochemistry. One of the following criteria must be detected:
- •If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L;
- •Or urine M protein level ≥200mg/24h;
- •Or light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal;
- •Or there are extramedullary lesions;
- •Subjects who have received at least 3 different mechanism drugs (including chemotherapy, protease inhibitors, immunosuppressive agents, etc.) have failed treatments, or have progressed or recurred during the last treatment or within 6 months after the end of treatment ;
- •Lung function is normal, and oxygen saturation is greater than 92%;
- •No heart disease or coronary heart disease, echocardiogram showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious arrhythmia;
- •Liver function: TBIL<3×ULN, AST<2.5×ULN, ALT<2.5ULN;
- •Renal function: creatinine clearance rate (estimated by Cockcroft Gault formula) ≥ 30 mL/min;
- •The blood routine meets the following standards:
- •Lymphocyte count>0.5×10e9/L;
- •Neutrophils ≥1.0×10e9/L;
- •Hemoglobin ≥80g/L;
- •Platelet ≥75×10e9/L
- •From the use of study drug to 2 years after treatment, male subjects or female subjects of childbearing age must agree and be able to take effective contraceptive measures.
排除标准
- •Pregnant or breastfeeding;
- •HBsAg or HBcAb are positive, and the quantitative detection of HBV DNA in peripheral blood is more than 100 copies / L; HCV antibody and HCV RNA in peripheral blood are positive; HIV antibody positive; Syphilis antibody is positive in the first screening;
- •Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade III), severe arrhythmia with poor drug control, liver, kidney or metabolic diseases;
- •Had hypersensitivity or intolerance to any drug used in this study;
- •Patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening;
- •Uncontrolled malignant tumors except MM, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment;
- •Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis;
- •In the past two years, autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs, or required systemic application of immunosuppressive or other drugs;
- •Severe active viral, bacterial or uncontrolled systemic fungal infections; Hereditary bleeding / coagulation diseases, history of non traumatic bleeding or thromboembolism, other diseases that may increase the risk of bleeding, etc;
- •Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period;
- •Patients received allogeneic stem cell therapy;
- •Any unsuitable to participate in this trial judged by the investigator.
研究组 & 干预措施
Treatment Group
Experimental
This is a open label, single arm clinical trial.
干预措施: GPRC5D-CAR-T (Drug)
结局指标
主要结局
AE and SAE
时间窗: From admission to the end of the follow-up, up to 2 years
Adverse event and serious adverse event
Dose limited toxicity (DLT)
时间窗: From date of initial treatment to Day 28 post GPRC5D CAR-T infusion.
Dose limited toxicity
次要结局
- Concentration of CAR-T cells(From admission to the end of the follow-up, up to 2 years)
- Objective Response Rate, ORR(In 3 months of GPRC5D CAR-T cell infusion)
- Duration of remission, DOR(24 months post GPRC5D CAR-T cells infusion)
- Overall survival, OS(From GPRC5D CAR-T infusion to death，up to 2 years)
- Disease control rate, DCR(From Day 28 GPRC5D CAR-T infusion up to 2 years)
- Progression-free survival, PFS(24 months post GPRC5D CAR-Tcells infusion)
研究者
He Huang
Chief Physician
Zhejiang University
研究点 (1)
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