NCT06503224招募中不适用
An Exploratory Clinical Study of a Fourth-generation Autologous CAR-T Cell Injection (SCAR02) Targeting BCMA and CD19 for the Treatment of Refractory Autoimmune Diseases
The First Affiliated Hospital of University of Science and Technology of China1 个研究点 分布在 1 个国家目标入组 18 人开始时间: 2024年4月9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
- 18
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This is an open label, single-site, dose-escalation study in up to 18 participants with refractory autoimmune diseases. This study aims to evaluate the safety and efficacy of the treatment with Anti-BCMA and CD19 CART
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Sign the informed consent form.
- •At the time of signing the informed consent form, the age of 18 years old or above, both male and female.
- •Bone marrow hematopoietic function is satisfied: white blood cell count ≥3×10^9/L; neutrophil count ≥1×10^9/L (not receiving colony-stimulating factor within 2 weeks prior to screening); hemoglobin ≥60g/L.
- •Liver function fulfillment: ALT≤3×ULN; AST≤3×ULN; TBIL≤3×ULN.
- •Renal function fulfillment: creatinine clearance CrCl ≥ 60mL/min.
- •Coagulation function meets: international standard ratio INR <1.5 times ULN, prothrombin time PT <1.5 times ULN.
- •Patients with rheumatoid arthritis must also meet the following enrollment criteria:
- •Diagnosis of rheumatoid arthritis according to the 2010 ACR / EULAR diagnostic criteria.
- •Fulfillment of one of the following conditions: DAS28-ESR >3.2 or CDAI >10 at 3 months after use of a standard treatment regimen prior to screening; inability to taper hormones (prednisone) to less than 7.5 mg/day; and number of swollen joints and/or number of joints with tenderness ≥
- •Standard treatment regimen is defined as the stable use of any of the following (alone or in combination): corticosteroids, nonsteroidal anti-inflammatory drugs ( NSAIDs) and csDMARDs, including methotrexate, leflunomide, hydroxychloroquine, salazosulfapyridine, elamodex, tretinoin, and paeonia lactiflora total, as well as biological agents (including TNF inhibitors, non-TNF inhibitors, and JAK inhibitors).
- •Stable treatment with 1 or 2 cs DMARD(s) prior to enrollment as follows: at least 12 weeks of methotrexate and at least 4 weeks of administration at a dose of 7.5-25 mg/week; at least 4 weeks of stable hydroxychloroquine doses of ≤400 mg/d; at least 4 weeks of stable oral salicylazosulfapyridine 1 to 3 g/d; at least 4 weeks of stable oral leflunomide 10-20 mg /d.
- •Patients with SLE will also be required to meet the following enrollment criteria:
- •Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE.
- •A history of SLE for at least 6 months prior to screening, with the disease remaining active 2 months after the use of a standard treatment regimen prior to screening. Standard treatment regimen is defined as stable use of any of the following (alone or in combination): corticosteroids, antimalarials, nonsteroidal anti-inflammatory drugs (NSAIDs), and other immunosuppressive or biologic agents, including azathioprine, mertiomaxolide, cyclophosphamide, methotrexate, leflunomide, tacrolimus, cyclosporine, belimumab, rituximab, and tetracycline.
- •BILAG-2004 assessment of the presence of at least 1 grade A or 2 grade B organ scores.
- •Positive for at least one of the following antibodies: anti-nuclear antibody, anti-ds-DNA antibody, anti-Sm antibody.
- •SLEDAI-2000 score ≥ 8 during the screening period.
- •Patients with dry syndrome were also required to meet the following enrollment criteria:
- •Diagnosis of dry syndrome according to the 2002 International Classification Criteria for Primary Dry Syndrome or the 2016 ACR/EULAR classification criteria.
- •Diagnosis of pSS-TP with platelet count <30 x 10^9/L.
- •History of dry syndrome for at least 6 months prior to screening and disease still active 2 months after use of conventional treatment regimen prior to screening. Definition of conventional therapy:Use of glucocorticoids (above 1 mg/Kg/d) and cyclophosphamide, and any of the following immunomodulatory drugs for more than 6 months: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, and cyclosporine, as well as biologics, such as rituximab, belimumab, and tetraciprazole.
- •Patients with systemic sclerosis were also required to meet the following enrollment criteria:
- •Diagnosis of systemic sclerosis according to the 2013 ACR classification criteria for systemic sclerosis.
- •Positive antinuclear antibodies at screening.
- •Presence of clear evidence of HRCT progression.
- •History of systemic sclerosis for at least 6 months prior to screening, and active disease 2 months after use of a conventional treatment regimen prior to screening. Definition of conventional therapy:Use of glucocorticoids (above 0.5 mg/Kg/d) and cyclophosphamide for more than 6 months, as well as any of the following immunomodulatory medications: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, and cyclosporine, as well as biologics, such as rituximab and belimumab.
排除标准
- •pre-screening presence of clinically significant CNS disease or pathological changes not caused by the disease itself, including, but not limited to: stroke, apoplexy, aneurysm, epilepsy, convulsions, aphasia, severe craniocerebral injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, or insanity.
- •Those suffering from relatively serious heart diseases such as angina pectoris, myocardial infarction, heart failure and arrhythmia.
- •History of major organ transplantation or hematopoietic stem cell/bone marrow transplantation.
- •vaccination, B-cell targeted therapy within 4 weeks prior to screening.
- •History of any malignant disease.
- •Patients with end-stage renal failure.
- •Presence or suspected presence of uncontrolled fungal, bacterial, viral or other infections.
- •History of severe allergy to drugs used in clinical studies or raw materials of test drugs, such as cyclophosphamide, fludarabine, DMSO.
- •The patient is positive for HBV surface antigen, or HBV core antibody and positive for DNA by RT-PCR; positive for HCV antibody or positive for HIV antibody or positive for syphilis or positive for CMV DNA or positive for EBV DNA.
- •Females who are pregnant or breastfeeding or who plan to have a pregnancy within 2 years of return infusion of the test drug; partners of male patients who plan to become pregnant within 2 years of treatment with the test drug.
- •Evidence of active tuberculosis infection.
- •other circumstances assessed by the investigator as unsuitable for enrollment.
研究组 & 干预措施
Anti-BCMA and CD19 CART
Experimental
Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of Anti-BCMA and CD19 CART will be infused on day 0.
干预措施: Anti-BCMA and CD19 CART cells will be injected intravenously on a one-time basis. (Drug)
结局指标
主要结局
Adverse events
时间窗: up to 2 years
Total number, incidence and severity of adverse events (AEs) in patients of SCAR02 infusion. The AEs will be assessed according to the 2019 Consensus on Cytokine Release Syndrome and Immune-cell-associated Neurotoxicity published by the American Society of Transplantation and Cell Therapy (ASTCT), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and EBMT 2019 consensus.
次要结局
- The persistence, accumulation, and migration of Anti-BCMA and CD19 CART cells(up to 2 years)
- Visual Analogue Scale(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000) from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Erythrocyte Sedimentation Rate(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- American College of Rheumatology (ACR) criteria 20, 50, 70 response rate(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Swollen and tender joint count(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in the Physician Global Assessment (PGA) score from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in the BILAG-2004 score from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in immunological indexes from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in level of anti-nuclear antibody (ANA) in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in level of anti-double stranded DNA (dsDNA) antibody in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in levels of complement in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in levels of anti-Ro/SSA antibodies in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in levels of Changes in levels of anti-Ro/SSA antibodies in peripheral blood from baseline in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in levels of Changes in levels of RF in peripheral blood from baseline in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in levels of Changes in levels of anti-topoisomerase I antibody in peripheral blood from baseline in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
- Changes in levels of Changes in levels of anti-RNA polymerase III antibody in peripheral blood from baseline in peripheral blood from baseline(Day-1, 14, 21, 28 and Month2, 3, 6, 9, 12, 18, 24)
研究者
研究点 (1)
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