A Phase I Clinical Study of SL4903 Autologous T-Cell Injection for the Treatment of Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 9
- 主要终点
- Number and incidence rate of adverse events following intravenous infusion of SL4903 cells
研究概览
简要总结
This is a Phase I, single-center, single-arm, open-label clinical study to evaluate the safety, tolerability, and preliminary efficacy of SL4903 autologous T-cell injection (CAR-T cell therapy) in adult patients with relapsed or refractory multiple myeloma (r/r MM) who have failed prior standard therapies.
The study employs a "3+3" dose-escalation design with three planned dose levels (1×10⁶, 2×10⁶, and 3×10⁶ CAR+ cells/kg). Approximately 9 to 18 evaluable subjects will be enrolled to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D), and to characterize the safety profile and potential anti-myeloma activity of SL4903.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subjects must meet ALL of the following conditions:
- •Age 18-75 years; either sex.
- •Able to understand the study and provide voluntary written informed consent.
- •Histologically and/or cytologically confirmed multiple myeloma according to IMWG 2016 criteria, meeting the following conditions:
- •Patients must have received at least one prior line of anti-myeloma therapy, including treatment with proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies, or patients with multiple myeloma refractory to proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies;
- •Documented evidence of disease progression or failure to achieve complete response (CR) following the last line of therapy, as assessed by the investigator according to IMWG criteria.
- •Measurable disease at screening, defined as meeting one or more of the following criteria:
- •Serum M-protein ≥0.5 g/dL
- •Urinary M-protein ≥200 mg/24 h
- •Abnormal serum FLC ratio (<0.26 or >1.65) with involved FLC ≥10 mg/dL
- •Soft tissue extramedullary disease (EMD) identified by radiographic imaging with a longest diameter ≥ 2 cm
- •ECOG performance status 0-
- •Adequate organ function:
- •Serum creatinine ≤150 µmol/L or calculated creatinine clearance (Cockcroft-Gault) ≥40 mL/min (may be relaxed for acute MM-related renal impairment at investigator discretion).
- •Total bilirubin ≤2×ULN; ALT ≤3×ULN; AST ≤3×ULN.
- •Normal diastolic function on echocardiography, LVEF ≥50 %, no significant arrhythmia.
- •No active pulmonary infection; oxygen saturation on room air >90 %.
- •No contraindication to leukapheresis: Hemoglobin ≥ 60 g/L, platelets ≥ 50 × 10⁹/L, and lymphocytes ≥ 0.3 × 10⁹/L.
- •Life expectancy >12 weeks.
- •Women of child-bearing potential must have a negative urine pregnancy test and must not be breastfeeding; all men and women with reproductive potential must use effective contraception throughout the study.
排除标准
- •A subject will be excluded if ANY of the following apply:
- •History of severe immediate hypersensitivity to any study drug.
- •Central nervous system (CNS) disorders such as epilepsy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, or neuropathy (resolved cases without residual symptoms may be exempted at the investigator's discretion). Active CNS involvement, prior CNS myelomatous disease, or meningeal/spinal cord involvement signs must be excluded.
- •Prior traumatic brain injury, cerebrovascular accident, significant cerebral ischemia, or intracranial hemorrhage.
- •Concurrent uncontrolled malignancies other than adequately treated cervical carcinoma in situ, basal-cell or squamous-cell skin carcinoma, localized prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery, or thyroid cancer after curative surgery.
- •Clinically significant cardiovascular disease, e.g., uncontrolled or symptomatic arrhythmia, congestive heart failure, or NYHA class III/IV cardiac disease; myocardial infarction, coronary angioplasty/stenting, unstable angina, or other clinically relevant cardiac disorders within 12 months before enrollment.
- •Any severe comorbidity or condition judged by the investigator to increase subject risk or interfere with the study, including but not limited to liver cirrhosis or recent major trauma.
- •Prior BCMA- and/or GPRC5D-directed CAR-T therapy.
- •Allogeneic hematopoietic stem-cell transplantation within 6 months before screening, or any immunosuppressive therapy for graft-versus-host disease during screening.
- •Autoimmune disease, immunodeficiency, or need for immunosuppressants (except low-dose corticosteroids).
- •Uncontrolled active infection, including but not limited to active tuberculosis; suspected or proven uncontrolled fungal, bacterial, viral, or other infections.
- •Live attenuated vaccine within 4 weeks before leukapheresis.
- •Active hepatitis (HBV-DNA or HCV-RNA above the lower limit of detection), syphilis infection, congenital or acquired immunodeficiency including HIV, EBV or CMV viremia (DNA above the lower limit of detection).
- •History of alcohol abuse, drug abuse, or psychiatric illness.
- •Inability to meet the following washout requirements prior to PBMC collection:
- •Corticosteroids: no more than 5 mg prednisone (or equivalent) within 72 h.
- •Anti-tumor therapies: targeted therapy, epigenetic therapy, investigational drugs/devices-discontinued ≥14 days or ≥5 half-lives (whichever is longer); anti-myeloma monoclonal antibodies-≥21 days; cytotoxic therapy-≥14 days; proteasome inhibitors-≥14 days; immunomodulatory drugs-≥7 days.
- •Radiotherapy: completed ≥4 weeks before leukapheresis, except if the radiation field covers ≤5 % of marrow reserves.
- •Anti-T-cell antibodies (e.g., alemtuzumab): discontinued ≥8 weeks.
- •Any condition judged by the investigator to render the subject unsuitable for enrollment.
研究组 & 干预措施
Arm 1: dosage 1×10⁶ CAR⁺ cells/kg
In this dosage cohort (1×10⁶ CAR⁺ cells/kg). A total of 3-6 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and to determine the maximum tolerated dose (MTD).
Dose-Escalation Rules
• In the "3 + 3" phase, one subject is enrolled into each dose level and observed for 28 days after cell infusion (the observation period may be prolonged at the investigator's discretion).
干预措施: SL4903 Autologous T-Cell Injection (Drug)
Arm 2: dosage 2×10⁶ CAR⁺ cells/kg
In this dosage cohort (2×10⁶ CAR⁺ cells/kg). A total of 3-6 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and to determine the maximum tolerated dose (MTD).
Dose-Escalation Rules
• In the "3 + 3" phase, one subject is enrolled into each dose level and observed for 28 days after cell infusion (the observation period may be prolonged at the investigator's discretion).
干预措施: SL4903 Autologous T-Cell Injection (Drug)
Arm 3: dosage 3×10⁶ CAR⁺ cells/kg
In this dosage cohort (3×10⁶ CAR⁺ cells/kg). A total of 3-6 subjects are expected to be enrolled to evaluate the safety and tolerability of SL4903 autologous T-cell injection and to determine the maximum tolerated dose (MTD).
Dose-Escalation Rules
• In the "3 + 3" phase, one subject is enrolled into each dose level and observed for 28 days after cell infusion (the observation period may be prolonged at the investigator's discretion).
干预措施: SL4903 Autologous T-Cell Injection (Drug)
结局指标
主要结局
Number and incidence rate of adverse events following intravenous infusion of SL4903 cells
时间窗: one month
Within one month after cell infusion, all documented adverse events-including cytokine-release syndrome and neurotoxicity-will be analyzed for incidence, frequency, and severity to evaluate the safety of SL4903 and to determine the maximum tolerated dose (MTD).
次要结局
- Overall Survival (OS)(Minimum of 2 years post SL4903 CAR-T infusion)
- proportion of peripheral plasma cells(at day0 , day7, day10, day14 and day28 after CAR-T infusion)
- Overall response rate (ORR)(at 3, 6, 9, 12, 18, and 24-month after CAR-T infusion)
- Time to Response (TTR)(Minimum of 2 years post SL4903 CAR-T infusion)
- Pharmacokinetic (Tmax)(at day0 to day28 after CAR-T infusion)
- Complete response rate (CRR)(at 3, 6, 9, 12, 18, and 24-month after CAR-T infusion)
- Progression-free Survival (PFS)(Minimum of 2 years post SL4903 CAR-T infusion)
- Minimal Residual Disease (MRD) negative rate(at 3, 6, 9, 12, 18, and 24-month after CAR-T infusion)
- Pharmacokinetic (Cmax)(at day0 to day28 after CAR-T infusion)
- cytokines level(at day0 , day7, day10, day14 and day28 after CAR-T infusion)
- Duration of Response (DOR)(Minimum of 2 years post SL4903 CAR-T infusion)
- Pharmacokinetic (AUCday0~28)(at day0 to day28 after CAR-T infusion)