Exploratory Clinical Study Protocol on the Safety and Efficacy of Fully Human BCMA-Targeted Chimeric Antigen Receptor Autologous T-Cell Injection (IASO104) for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 主要终点
- incidence and severity of adverse events (AEs)
研究概览
简要总结
This study is a single-center, open-label, dose-exploration trial designed to evaluate the tolerability and safety of different doses of IASO104 in patients with relapsed/refractory plasma cell neoplasms, determine the recommended dose of IASO104, and assess its pharmacokinetic and pharmacodynamic characteristics. Additionally, the study will preliminarily observe the efficacy of the investigational drug in a small sample of subjects with relapsed/refractory multiple myeloma.
详细描述
This study adopts a "3+3" dose-escalation design, with three predefined dose levels: 0.5×10⁶ CAR-T cells/kg, 1.0×10⁶ CAR-T cells/kg, and 3.0×10⁶ CAR-T cells/kg, administered as a single infusion.For each dose group, the first subject must be observed for at least 2 weeks after infusion before subsequent subjects can be treated. If stable biological activity or clinical benefit is observed at a lower dose level, the study may proceed with 1-2 expanded dose groups at lower levels after discussion between the investigator and sponsor, without requiring MTD determination.During the dose-escalation phase, 2-3 subjects will be enrolled per dose level, with the total number of subjects depending on the escalation progression (estimated 4-6 subjects in this phase). Treatment in the next dose group may only begin after all subjects in the current group have completed DLT assessment post-infusion.
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
- •Age 18-75 years, any gender.
- •Diagnosis of multiple myeloma (MM) per International Myeloma Working Group (IMWG) diagnostic criteria.
- •Prior therapy requirements:
- •MM patients: ≥3 prior lines of therapy, including:
- •1 proteasome inhibitor (PI)
- •1 immunomodulatory drug (IMiD)
- •1 anti-CD38 monoclonal antibody Exception: No minimum line requirement for subjects refractory to PIs, IMiDs, and anti-CD38 therapy.
- •Primary plasma cell leukemia (pPCL): ≥1 prior line including ≥1 PI and ≥1 IMiD.
- •Documented disease progression during/within 12 months after last anti-myeloma therapy (exemption: No 12-month requirement if last line was CAR-T).
- •Measurable disease at screening (≥1 of the following):
- •Serum M-protein:
- •IgG ≥10 g/L IgA/IgD/IgE/IgM ≥5 g/L Urine M-protein ≥200 mg/24h Serum free light chains (FLC): Involved FLC ≥100 mg/L with abnormal κ/λ ratio Bone marrow plasma cells ≥30% (if no measurable M-protein/FLC).
- •ECOG performance status 0-
- •Life expectancy ≥12 weeks.
- •Adequate organ function (all lab values within 7 days prior to enrollment):
- •Hematology:
- •Absolute neutrophil count (ANC) ≥1×10⁹/L (allowed: growth factor support, but none within 7 days) Absolute lymphocyte count (ALC) ≥0.3×10⁹/L Platelets ≥50×10⁹/L (no transfusion within 7 days) Hemoglobin ≥60 g/L (no RBC transfusion within 7 days; erythropoietin allowed)
- •ALT/AST ≤2.5×ULN Total bilirubin ≤1.5×ULN Renal: Calculated CrCl ≥40 mL/min (Cockcroft-Gault)
- •Coagulation:
- •Fibrinogen ≥1.0 g/L aPTT/PT ≤1.5×ULN Pulmonary: SpO₂ >91% (room air) Cardiac: LVEF ≥50% (echocardiography).
- •Contraception: Subjects/partners must use effective contraception from consent through 1 year post CAR-T infusion (excluded: calendar method).
- •Signed informed consent approved by the Ethics Committee prior to screening.
排除标准
- •Active graft-versus-host disease (GVHD) or requiring long-term immunosuppressive therapy.
- •Prior hematopoietic stem cell transplantation (HSCT):
- •Autologous HSCT (Auto-HSCT) within 12 weeks before apheresis,
- •≥2 prior Auto-HSCTs, Any prior allogeneic HSCT (Allo-HSCT).
- •Prior cell therapy targeting plasma cells within 3 months before apheresis, or detectable residual cellular therapy products in peripheral blood.
- •Recent anti-myeloma therapies (relative to apheresis):
- •Monoclonal antibody treatment within 21 days, Cytotoxic chemotherapy or proteasome inhibitors within 14 days, Immunomodulatory drugs within 7 days, Other anti-tumor therapies within 14 days or 5 half-lives (whichever is shorter).
- •Chronic corticosteroid use (>20 mg/day prednisone or equivalent), except for physiologic replacement, topical, or inhaled use.
- •Uncontrolled hypertension despite medication.
- •Severe cardiac disease, including:
- •Unstable angina, Myocardial infarction (within 6 months before screening), Congestive heart failure (NYHA Class ≥III), Severe arrhythmias.
- •Unstable systemic illnesses per investigator's judgment (e.g., severe hepatic, renal, or metabolic disorders requiring medication).
- •Other malignancies within 5 years, excluding:
- •Carcinoma in situ of the cervix, Basal/squamous cell skin cancer, Localized prostate cancer post-radical resection, Ductal breast carcinoma in situ post-resection.
- •History of solid organ transplantation.
- •Suspected or confirmed CNS involvement by plasma cell neoplasms.
- •Major surgery within 2 weeks before apheresis or planned within 2 weeks post-treatment (allowed: minor procedures under local anesthesia).
- •Investigational drugs within 1 month before apheresis.
- •Uncontrolled active infections:
- •Persistent symptoms despite appropriate therapy, Requiring IV antimicrobials at screening.
- •Viral infections:
- •HBV: HBsAg(+) or HBcAb(+) with detectable HBV DNA, HCV: HCV Ab(+) with detectable HCV RNA, HIV Ab(+), CMV DNA(+), Syphilis: TRUST(+) and TPPA(+).
- •Pregnancy or lactation.
- •Psychiatric disorders, cognitive impairment, or active CNS diseases.
- •Other conditions deemed ineligible by the investigator.
研究组 & 干预措施
CT103d
CT103d will be administered in one infusion.
干预措施: CT103d (Biological)
结局指标
主要结局
incidence and severity of adverse events (AEs)
时间窗: Minimum 2 years after CT103d infusion
次要结局
- Overall Response Rate (ORR)(Minimum 2 years after CT103d infusion)
- Duration of Response (DOR)(Minimum 2 years after CT103d infusion)
- Progression-Free Survival (PFS)(Minimum 2 years after CT103d infusion)
- Overall Survival (OS)(Minimum 2 years after CT103d infusion)
- Time to Response (TTR)(Minimum 2 years after CT103d infusion)
- Time to Complete Response (TTCR)(Minimum 2 years after CT103d infusion)
- Minimal Residual Disease (MRD)-negative rate(Minimum 2 years after CT103d infusion)
- Duration of MRD Negativity(Minimum 2 years after CT103d infusion)
- Pharmacokinetic (PK) Endpoints(Minimum 2 years after CT103d infusion)
- Pharmacodynamic (PD) Endpoints(Minimum 2 years after CT103d infusion)