A Clinical Study to Evaluate the Safety, Tolerance and Efficacy of LCAR-M61SQ Cell in Patients with Relapsed/Refractory Multiple Myeloma.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 35
- 主要终点
- Dose-limiting toxicity (DLT) rate.
研究概览
简要总结
A prospective, open-label dose-exploration and expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor efficacy characteristics of LCAR-M61SQ in patients with relapsed/refractory multiple myeloma.
详细描述
This study is a prospective, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics, and antitumor efficacy characteristics of LCAR-M61SQ in patients with relapsed/refractory multiple myeloma. All subjects who meet the eligibility criteria will receive intravenous injection of LCAR-M61SQ cell injection. The study will include the following sequential phases: screening, apheresis, pre-treatment (lymphodepleting chemotherapy), treatment, and follow-up.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects voluntarily participate in clinical research;
- •Age ≥18 years old;
- •Eastern Cooperative Oncology Group (ECOG) score 0-2;
- •Examination evidence of initial diagnosis of MM according to IMWG diagnostic criteria;
- •Measurable lesions were present;
- •Subjects have received at least three previous lines of multiple myeloma therapy, each with at least one complete therapy cycle, unless the best response to the therapeutic regimen was documented as disease progression (PD confirmed according to IMWG criteria);
- •Expected survival ≥3 months;
- •Clinical laboratory values in the screening period meet criteria;
排除标准
- •Received previous therapy targeting GPRC5D targets;
- •Prior antineoplastic therapy and meet exclusion criteria (before apheresis);
- •Subjects had Waldenstrom macroglobulinemia, POEMS syndrome, or primary AL amyloidosis at the time of screening.
- •Subjects who were positive for any of HBsAg, HBV DNA, HCV-Ab, HCV RNA, and HIV-Ab;
- •Life-threatening allergic reactions, hypersensitivity reactions, or intolerance to CAR-T cell formulations or their excipients, including DMSO, are known.
- •Serious underlying diseases were present;
- •Female subjects who were pregnant, breastfeeding, or planning to become pregnant while participating in this study or within 1 year of receiving study treatment.
- •Also enrolled in other clinical studies.
研究组 & 干预措施
LCAR-M61SQ
Each subject will be given a single-dose LCAR-M61SQ cells infusion at each dose level
干预措施: Cell injection (Biological)
结局指标
主要结局
Dose-limiting toxicity (DLT) rate.
时间窗: From LCAR-M61SQ cell infusion (Day 1) until the 30th day of follow-up period, assessed up to 30 days
DLT is classified according to the NCI-CTCAE V5.0 toxicity evaluation criteria and ASTCT consensus classification within 30 days after dose infusion (D1-D30), which is considered by the investigator or collaborator to be reasonably related to LCAR-M61SQ cell therapy.
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: From the date of signing ICF to the date (2 years after LCAR-M61SQcell infusion
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
To determine the recommended dose for phase II clinical trials (RP2D)
时间窗: through the last subject of DLT exploration completion, about 2years.
RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design.
Maximum concentration (Cmax)
时间窗: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The maximum observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Time to Cmax
时间窗: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The time it takes to reach the maximum concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Time to the last observed concentration
时间窗: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The time it takes to reach the last observed concentration of CAR positive T cells or transgene CAR copy number in peripheral blood.
Area Under the Curve (AUC) of the concentration
时间窗: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years
The exposure of CAR positive T cells or transgene CAR copy number in peripheral blood experienced by the subject in a certain time interval.
次要结局
- Objective Response Rate (ORR)(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Very Good Partial Response Rate（VGPR）(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Complete response（CR）(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Stringent complete response（sCR）(: From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Minimal residual disease (MRD) negative rate(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression，assessed about 2 years)
- Time-to-response（TTR）(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Duration of response（DOR）(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Progression-free survival（PFS）(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Overall survival（OS(From the 7th days before first dose of pretreatment with chemotherapy until the date of first documented progression or study completion，assessed about 2 years)
- Occurrence rate of antidrug antibody(From LCAR-M61SQ cells infusion until the date of first documented progression or study completion，assessed about 2 years)