A Clinical Study on the Safety of in Vivo-CAR-T Cell Immunotherapy Targeting BCMA/GPRC5D for the Treatment of Relapsed/Refractory Plasma Cell Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
研究概览
简要总结
This study aims to assess the safety profile of in vivo BCMA/GPRC5D-targeted CAR-T cell immunotherapy in patients with relapsed or refractory plasma cell neoplasms.
详细描述
This is a single-center, open-label, single-arm, prospective study designed to evaluate the safety of in vivo BCMA/GPRC5D-targeted CAR-T cell immunotherapy in patients with relapsed or refractory plasma cell neoplasms. The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy. Safety assessments primarily focus on potential adverse events (AEs) following infusion of SL4903 injection, including the number of cases, incidence rates, and severity of cytokine release syndrome, immune effector cell therapy-related neurotoxicity, hematologic toxicity, organ toxicity, ect. Efficacy assessments will include overall objective response rate (ORR), event-free survival (EFS), overall survival (OS), progression-free survival (PFS), duration of complete remission, relapse rate, and mortality rate. Exploratory analyses will focus on characterizing the in vivo kinetics of CAR-T cells and the clonal evolution of plasma cell neoplasms during and after consolidation treatment.
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
- •Voluntary signing of informed consent by the subject or legally authorized representative, with willingness and ability to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
- •Diagnosis of relapsed or refractory plasma cell neoplasms meeting the following criteria:
- •Clonal plasma cells confirmed to be BCMA and/or GPRC5D positive by flow cytometry or immunohistochemistry;
- •Previously treated with at least 2 lines of anti-plasma cell neoplasms therapy, with at least 1 complete treatment cycle for each line, and evidence of disease progression within 12 months after the most recent anti-plasma cell neoplasms treatment, or being refractory to both immunomodulatory drugs and proteasome inhibitors, with disease progression within 2 months after the most recent anti-plasma cell neoplasms treatment (according to the IMWG diagnostic criteria)
- •Age 18 to 75 years (inclusive), male or female.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Life expectancy > 3 months from the date of informed consent.
- •Hemoglobin (HGB) ≥ 60 g/L (transfusion allowed).
- •Adequate organ function (hepatic, renal, cardiac, and pulmonary):
- •Creatinine ≤ 2 × ULN;
- •Left ventricular ejection fraction (LVEF) ≥ 50%;
- •Oxygen saturation > 90%;
- •Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN.
- •Willingness to use highly effective contraception from signing of informed consent until 1 year after SL4903 infusion.
排除标准
- •Severe cardiac dysfunction with left ventricular ejection fraction (LVEF) < 50%.
- •History of severe pulmonary impairment.
- •Concurrent diagnosis of another active malignancy.
- •Uncontrolled active infection.
- •History of severe autoimmune disease or primary immunodeficiency.
- •Active hepatitis (defined as HBV DNA or HCV RNA above the lower limit of detection).
- •Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), or active syphilis.
- •History of severe hypersensitivity to biological products (including antibiotics).
- •Allogeneic hematopoietic stem cell transplant recipients with ongoing acute graft-versus-host disease (GVHD) despite discontinuation of immunosuppressive therapy for at least one month prior to screening.
- •Any other severe comorbidities or laboratory abnormalities that, in the investigator's opinion, would increase the risk to the subject or interfere with study results, rendering the subject unsuitable for participation.
- •Pregnant or breastfeeding women (including women of childbearing potential who are pregnant or lactating).
研究者
Liping Dou
Director
Chinese PLA General Hospital