NCT06614270招募中不适用
Clinical Study of Core Blood-derived Anti-CD19 IL-10/IL15 CAR-NK in the Treatment of Refractory/Relapsed Autoimmune Diseases
Second Affiliated Hospital, School of Medicine, Zhejiang University1 个研究点 分布在 1 个国家目标入组 15 人开始时间: 2025年1月6日最近更新:
适应症
干预措施
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The proportion of subjects with DLT
研究概览
简要总结
This study is a single-center, open-label, single-arm, dose-escalation trial. The aim of this study is to investigate the safety and efficacy of Anti-CD19 IL-10/IL15 CAR-NK cells in patients with refractory/relapsed autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myositis, ANCA associated vasculitis, sjogren syndrome, and antiphospholipid syndrome.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Combined with other connective tissue diseases;
- •Involvement of important organs: heart (individuals with more severe heart disease, such as angina, myocardial infarction, heart failure, and arrhythmias), kidney (eGFR < 15 ml/min/1.73m2), liver (ALT>3×ULN, AST>3×ULN, TBIL >1.5×ULN), lung (FVC<50% predicted or hemoglobin-corrected DLCO<40% predicted), hematologic (leukocyte < 2.5×109/L, neutrophil count <1.0×109/L, HGB<60g/L), etc.;
- •Abnormal hepatitis B or hepatitis C test indicating active infection or chronic infection, including positive HBsAg or HBcAb test and positive hepatitis C antibody;
- •Have active tuberculosis or latent tuberculosis;
- •Human immunodeficiency virus (HIV) serology positivity or known history of HIV infection;
- •Presence of any known serious active infection (including bacterial, viral, fungal, etc.), including those requiring hospitalization or intravenous antibiotic therapy within 4 weeks prior to screening and oral antibiotic therapy within 2 weeks prior to screening; Those who have various chronic infections and are currently receiving corresponding treatment, such as pneumocystosis, cytomegalovirus, herpes zoster, atypical mycobacteria, etc.;
- •Patients with primary or secondary immunodeficiency;
- •IgA deficiency (<10 mg/dL) or IgG deficiency (<400 mg/dL);
- •Receiving other investigational drug treatment or participating in any other drug trial within 3 months before screening;
- •History of documented and confirmed malignancy within 5 years prior to screening, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been appropriately treated or resected;
- •Patients who are pregnant, breastfeeding, or planning a recent pregnancy, or who are unwilling to use a reliable contraceptive method of contraception for the duration of the study;
- •Those who have been allergic to human or murine proteins and monoclonal antibodies in the past;
- •Received live vaccine or live attenuated vaccine within 4 weeks prior to randomization;
- •Patients who are not expected to comply with the requirements of the protocol or are not expected to complete the trial as planned (such as those with psychiatric disorders, history of alcoholism, drug or other substance abuse);
- •Other conditions that the investigator considers the patient not suitable to enter the trial.
- •Systemic Sclerosis Exclusion Criteria:
- •Localized cutaneous SSc;
- •the duration of the disease is greater than 5 years (defined as the onset of the first non-RP symptom);
- •SSc-like syndrome related to environmental factors, such as vinyl chloride, bleomycin, etc.;
- •Any history of scleroderma renal crisis;
- •intermediate- and high-risk pulmonary hypertension;
- •Active antral vasodilation.
- •Idiopathic Inflammatory myopathy exclusion criteria:
- •drug-induced myopathy;
- •inclusion body myositis;
- •Tumor-associated myositis (myositis occurring within 2 years of diagnosis of tumor).
- •ANCA-associated vasculitis exclusion criteria:
- •alveolar hemorrhage, requiring invasive lung ventilation, which is expected to last longer than the screening time;
- •Need for dialysis or plasmapheresis during screening;
- •Have undergone a kidney transplant.
- •Sjögren's syndrome exclusion criteria:
- •Combined with liver cirrhosis;
- •Combined with aplastic anemia (AA), myelodysplastic syndrome (MDS) or other myeloproliferative disorders (MPD);
- •drug-induced thrombocytopenia;
- •Thrombotic thrombocytopenic purpura (TTP)/microthrombotic vascular disease (TMA).
- •Antiphospholipid syndrome exclusion criteria:
- •Obstetric APS;
- •APS incorporates other CTDs;
- •APS involves the nervous system.
研究组 & 干预措施
Participant Group
Experimental
Anti-CD19 IL-10/IL15 CAR-NK
干预措施: Anti-CD19 IL-10/IL15 CAR-NK (Drug)
结局指标
主要结局
The proportion of subjects with DLT
时间窗: Within 28 days after anti-CD19 CAR-NK cells infusion
DLT definition is dose-limiting toxicity.
The proportion of subjects with adverse events
时间窗: 12 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs as assessed by CTCAE v5.0.
次要结局
- Changes in SLEDAI-2K scores and the proportions of patients achieving SRI-4 response, DORIS remission, and LLDAS in systemic lupus erythematosus.(12 months)
- changes of mRSS score for systemic sclerosis(48 weeks)
- definition of improvement by IMACS for IIM(48 weeks)
- STAR score for sjogren's syndrome(48 weeks)
- BVAS for AAV(48 weeks)
- Thrombosis/death for APS(48 weeks)
研究者
研究点 (1)
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