An Investigator-initiated Trial Evaluating the Efficacy and Safety of Anti-GPRC5D CAR-T Cells Therapy in the Treatment of Relapsed / Refractory(r/r) Multiple Myeloma(MM)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Incidence of adverse events(AE) after infusion
研究概览
简要总结
It is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-GPRC5D CAR-T cells therapy for relapsed and refractory(r/r) multiple myeloma(MM).
详细描述
This open label, single-arm, Phase I study aims to evaluate the efficacy and safety of Anti-GPRC5D CAR-T in subjects with relapsed and refractory(r/r) multiple myeloma(MM). A leukapheresis procedure will be performed to manufacture Anti-GPRC5D chimeric antigen receptor (CAR) modified T cells. Prior to Anti-GPRC5D CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.
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
- •The patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure;
- •Age 18-75 years old, gender unlimited;
- •Patients diagnosed with multiple myeloma according to International Myeloma Working Group(IMWG) diagnostic criteria;
- •Subjects who had failed treatment with at least 3 drugs of different mechanisms (including chemotherapy, proteasome inhibitors, immunomodulators, etc.), or had progressed or relapsed during the last treatment period or within 6 months after the end of treatment;
- •The presence of measurable lesions at screening was determined according to any of the following criteria, defined as: (1) serum monoclonal immunoglobulin (M-protein) level ≥1.0 g/dL; (2) urine M protein level ≥200 mg/ 24h; (3) Light chain multiple myeloma diagnosed with no measurable lesion in serum or urine: serum immunoglobulin free light chain ≥10 mg/dL and serum immunoglobulin κ/γ free light chain ratio abnormal;
- •The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade < 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy);
- •Eastern cooperative oncology group (ECOG) score is 0-2;
- •Survival is expected to be greater than 3 months;
- •Adequate liver , kidney and cardiopulmonary function;
- •Willingness to complete the informed consent process and to comply with study procedures and visit schedule.
排除标准
- •Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma;
- •Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter;
- •It is suspected that MM has involved the central nervous system or meninges and has been confirmed by MRI or CT, or there are other active central nervous system diseases;
- •Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis;
- •HBsAg or HBcAb are positive, and the quantitative detection of hepatitis B virus(HBV) DNA in peripheral blood is more than 100 copies / L;hepatitis C virus (HCV) antibody and HCV RNA in peripheral blood are positive; HIV antibody positive; Syphilis antibody is positive in the first screening;
- •Pregnant or breastfeeding;
- •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;
- •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;
- •Persons with serious mental illness;
- •Alcoholics or persons with a history of drug abuse;
- •Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
- •Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening;
- •Any unsuitable to participate in this trial judged by the investigator.
结局指标
主要结局
Incidence of adverse events(AE) after infusion
时间窗: Up to 12 months after infusion
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. Description, time, classification, and outcome of AE events resulted from the investigational medical product, delivery method, or emergency measures will be recorded in the case report form.
Dose limited toxicity (DLT)
时间窗: Up to 1 month after infusion
Dose limited toxicity(DLT) was defined as the occurrence of any of the following adverse events within 28 days of the infusion of CAR-T cells after optimal supportive treatment, which were discussed with the investigator and determined to be associated or likely to be associated with the infusion.
次要结局
- Progression-free survival(PFS)(Up to 2 years)
- Overall Response Rate (ORR)(Up to 2 years after infusion)
- Concentration of CAR-T cells(Days 4, 7, 10, 14 and months 2, 3, 6, 9, 12 after infusion)
- Overall survival(OS)(Up to 2 years)