Clinical Study on the Safety and Efficacy of CAR BCMA-CD70 Dual-target CAR-T Therapy for High-risk Plasma Cell Neoplasms
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safety of CAR BCMA-CD70 CAR-T cells in the treatment of CD70/BCMA positive high-risk plasma cell neoplasms.
研究概览
简要总结
This is a single arm study to evaluate the safety and efficacy of CAR BCMA-CD70 CAR-T cell therapy for high-risk plasma cell neoplasms.
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 or their legally acceptable representative has provided written informed consent and is willing and able to comply with all scheduled study visits, study treatment administration, laboratory tests, and other required trial procedures.
- •Clinically diagnosed with high-risk plasma cell neoplasm, meeting any one of the following molecular/cytogenetic or clinical criteria:
- •Deletion of the short arm of chromosome 17 (del(17p)) with clonal proportion ≥ 20%, and/or TP53 gene mutation;
- •IgH translocation (t(4;14), t(14;16), or t(14;20)) combined with 1q amplification (1q+) and/or deletion of the short arm of chromosome 1 (del(1p32));
- •Chromosome 1 abnormalities: monoallelic del(1p32) plus 1q+, or biallelic del(1p32);
- •β₂-microglobulin ≥ 5.5 mg/L with normal serum creatinine (< 1.2 mg/dL).
- •Age 18 to 75 years (inclusive), male or female.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Life expectancy > 3 months from the date of signed informed consent.
- •Hemoglobin (HGB) ≥ 60 g/L (transfusion permitted).
- •Adequate hepatic, renal, and cardiopulmonary function as defined by:
- •Serum creatinine ≤ 2 × ULN;
- •Left ventricular ejection fraction (LVEF%) ≥ 50%;
- •Blood oxygen saturation > 90%;
- •Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN.
- •Subject agrees to use highly effective contraception from the date of informed consent until 1 year after CAR-T cell infusion.
排除标准
- •Severe cardiac insufficiency with left ventricular ejection fraction (LVEF%) < 50%.
- •History of severe chronic lung disease associated with impaired pulmonary function.
- •Concurrent active or progressive malignant tumors other than the target plasma cell neoplasm.
- •Concurrent severe infection that cannot be effectively controlled with standard therapy.
- •Concurrent severe autoimmune disease or congenital immunodeficiency disorders.
- •Active viral hepatitis, defined as hepatitis B virus DNA (HBV-DNA) or hepatitis C virus RNA (HCV-RNA) levels above the lower limit of detection (LLOD).
- •Human immunodeficiency virus (HIV) infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection.
- •History of severe allergic reactions to biological products, including antibiotics.
- •Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with persistent acute graft-versus-host disease (aGVHD) that does not resolve within 1 month after discontinuing immunosuppressive therapy.
- •Presence of other severe physical or psychiatric illnesses, or significant laboratory abnormalities, that may increase the risks of study participation, interfere with study outcomes, or render the subject otherwise unsuitable for enrollment as determined by the investigator.
- •Female subjects of childbearing potential who are pregnant or breastfeeding.
研究组 & 干预措施
This is a single arm treatment of CAR BCMA-CD70 CAR-T cell
Experimental: CAR BCMA-CD70 T cells Therapy. Investigational product: CAR BCMA-CD70 T cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of BCMA-CD70-CAR-T cells.
干预措施: CAR BCMA-CD70-T cells (Genetic)
This is a single arm treatment of CAR BCMA-CD70 CAR-T cell
Experimental: CAR BCMA-CD70 T cells Therapy. Investigational product: CAR BCMA-CD70 T cells. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: A combination of fludarabine and cyclophosphamide will be administered prior to the infusion of BCMA-CD70-CAR-T cells.
干预措施: fludarabine and cyclophosphamide (Drug)
结局指标
主要结局
According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safety of CAR BCMA-CD70 CAR-T cells in the treatment of CD70/BCMA positive high-risk plasma cell neoplasms.
时间窗: MTD will be determined based on DLTs observed during the first 28 days of study treatment
According to the incidence of treatment-related adverse events (AEs) to evaluate the safetyof CAR BCMA-CD70 CAR-T cells in the treatment of CD70/BCMA positive high-risk plasma cell neoplasms.
时间窗: up to 3 years
Incidence of treatment-related adverse events (AEs) Description: Number and severity of adverse events graded according to CTCAE v5.0, including cytokine release syndrome (CRS) graded by ASTCT criteria and immune effector cell-associated neurotoxicity syndrome (ICANS) graded by ASBMT criteria
次要结局
- According to the objective response rate (ORR) to evaluate the efficacy of CAR BCMA-CD70 CAR-T cells in the treatment of CD70/BCMA positive high-risk plasma cell neoplasms.(Within 3 months following infusion of CAR BCMA-CD70 CAR-T cells)