NCT05913804招募中1 期
An Exploratory Clinical Study on the Safety and Efficacy of YTS104 Cell Injection in the Treatment of Relapsed or Refractory Multiple Myeloma
Institute of Hematology & Blood Diseases Hospital, China1 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2023年6月28日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Patients with Dose Limiting Toxicity
研究概览
简要总结
This is a single-center, single-arm, open-label phase I clinical study to determine the safety and efficacy of relapsed or refractory multiple myeloma subjects
详细描述
This study will recruit multiple myeloma subjects,and Subjects should undergo FC chemotherapy before returning the cells, then followed by infusion of YTS104 cells injection. YTS104 cells injection will be intravenously infused with a escalated dose of 1E6#3E6#6E6#1E7 cells/kg.
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
- •Aged 18-75 years, gender is not limited;
- •Patients diagnosed as relapsed/refractory multiple myeloma according to the International Myeloma Working Group (IMWG 2014) criteria for multiple myeloma after at least 3 lines of treatment (including at least one proteasome inhibitor and an immunomodulator based chemotherapy regimen), and at least one complete treatment cycle per line of treatment; Documented disease progression during or within 12 months after the most recent antimyeloma therapy (not limited to 12 months after CAR-T therapy as the last line of therapy);
- •The presence of one or more measurable lesions at screening was defined as any of the following: 1) serum M-protein ≥0.5g/dL (≥5g/L), 2) urinary M-protein level ≥200 mg/24 hours; 3) serum free light chain (sFLC) ≥100 mg/L and serum κ/λ free light chain ratio abnormal (<0.26 or >1.65);
- •Good organ function;
- •ECOG score ≤1;
- •The predicted survival time was ≥12 weeks;
- •Female subjects of childbearing age or male subjects with partners of women of childbearing age agreed to use effective methods of contraception throughout the trial and for 12 months after cell infusion;
- •The subjects voluntarily participated in the study, signed the informed consent form, and complied with the follow-up.
排除标准
- •A history of allergy to any component of the cell product;
- •Patients who had used CAR-T cell therapy or any other gene transduction or other therapeutic products within 3 months after signing the informed consent, except those with undetectable CAR-T cells or CAR-T cells below the lower limit of detection;
- •Subjects had plasma cell leukemia, Waldenström's macroglobulinaemia, POEMS syndrome, or primary light chain amyloidosis;
- •Patients with a history of any of the following cardiovascular and cerebrovascular diseases within the preceding 6 months were screened;
- •Congestive heart failure (New York Heart Association [NYHA]≥III), congenital long QT syndrome, left front half block (double bundle block), asymptomatic right bundle branch block allowed; Myocardial infarction, unstable angina pectoris, coronary angioplasty, stent implantation, coronary/peripheral artery bypass grafting;
- •Cerebrovascular accident (CVA) and transient ischemic attack (TIA);
- •Severe arrhythmias requiring treatment (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, etc.); d: Subjects had uncontrolled hypertension (systolic blood pressure greater than 160 mmHg and/or diastolic blood pressure greater than 100 mmHg), a history of hypertensive crisis, or hypertensive encephalopathy;
- •Pulmonary embolism, or deep venous thrombosis of the lower extremity requiring anticoagulation, or active lung disease and/or pneumonia have occurred within 6 months prior to screening;
- •Hepatitis B surface antigen (HBsAg) positive; Hepatitis B core antibody (HBcAb) and HBV DNA in peripheral blood were positive. Hepatitis C virus (HCV) antibody positive and HCV RNA positive; Treponema pallidum antibody was positive;
- •Patients with known systemic lupus erythematosus, co-active or uncontrolled autoimmune diseases (e.g., Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.), primary or secondary immunodeficiency (e.g., HIV infection or severe infectious diseases);
- •Patients with previous or concurrent uncured malignant tumors with unstable control, affecting the long-term survival of the subjects, excluding cured cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer, or other malignant tumors with local prostate cancer after radical treatment, ductal carcinoma in situ after radical treatment and no recurrence for at least 5 years;
- •Patients with current or previous history of central nervous system disease, such as seizures, stroke, severe brain injury, aphasia, paralysis, dementia, Parkinson's disease, mental illness, etc.;
- •Have central nervous system (CNS) involvement or symptoms of CNS involvement (including cranial neuropathy and extensive lesions or spinal cord compression);
- •Patients had undergone previous solid-organ transplantation or allogeneic hematopoietic stem-cell transplantation (allo-HSCT) 6 months before screening or autologous stem-cell transplantation within 3 months before apheresis;
- •Patients with acute or chronic graft-versus-host disease (GVHD) at screening time;
- •The following anti-MM treatments were used at the indicated times prior to apheresis:
- •Use of any immunosuppressant or radiotherapy within 2 weeks prior to apheresis;
- •Received cytotoxic or proteasome inhibitors or small-molecule targeted therapy within 2 weeks of preapheresis or 3 half-lives, whichever is shorter;
- •Received any macromolecular therapy such as monoclonal antibodies within 4 weeks prior to anapheresis or within 3 half-lives, whichever is shorter;
- •Received immunomodulator within 1 week;
- •The patient had a history of live vaccination within 4 weeks before signing ICF;
- •Subjects had a history of mental illness, or substance abuse;
- •Subjects were pregnant or lactating;
- •If participating in other interventional clinical studies before apheresis, the requirements of drug washout before apheresis should be met;
- •The investigator believes that there are other factors unsuitable for inclusion or affecting participants' participation in or completion of the study.
研究组 & 干预措施
YTS104 cells injection
Experimental
Subjects will receive cell infusion, with the initial cell dose of 1E6/kg. 1-6 subjects will be enrolled. The second dose group was 3E6 cells /kg with 1-6 subjects; The third and fourth dose groups were 6E6 cells /kg and 1E7 cells /kg, respectively, with 3-6 subjects.Subjects may undergo secondary or multiple retransfusion
干预措施: YTS104 Cells injection (Biological)
结局指标
主要结局
Number of Patients with Dose Limiting Toxicity
时间窗: Within 28 days after cell transfusion
Dose-limiting toxicity was defined as adverse events associated with YTS104-cell injection within 28 days of cell transfusion, including grade 4 or 5 CRS and ICANS; grade 4 haematological adverse events did not return to grade 2 or baseline within 28 days of cell transfusion
Incidence and severity of adverse events
时间窗: 24 months
After YTS104-cell infusion, adverse events will be graded as CTCAE 5.0
次要结局
- Overall response rate (ORR)(24 months)
- Duration OF RESPONSE(DOR)(24 months)
- Expansion and persistence of YTS104 cell injection in vivo(24 months)
- Progression-free survival(PFS)(24 months)
- Overall survival(OS)(24 months)
研究者
研究点 (1)
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