肿瘤细胞治疗研究
英文原题：Anti CD19/BCMA CAR Gene Therapy for Relapsed/Refractory Immune Thrombocytopenia
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本开放标签、单中心剂量递增研究评估LCAR1901抗CD19/BCMA CAR基因载体注射治疗复发/难治性原发免疫性血小板减少症的安全性和疗效，计划入组最多18名患者。
不限性别 · ≥ 18 Years
纳入标准： 1. 年龄≥18岁，性别不限。 2. 原发免疫性血小板减少症（ITP）临床诊断至少6个月；研究前48小时内血小板<30×10⁹/L。 3. 抗血小板糖蛋白自身抗体（如GPIIb/IIIa）阳性。 4. 既往接受二线ITP治疗后无效、复发或停药后难以维持疗效。二线治疗包括TPO受体激动剂（如艾曲泊帕、罗米司亭）和/或利妥昔单抗；一线治疗为糖皮质激素或免疫球蛋白。无效指治疗后血小板<30×10⁹/L、未较基线上升至2倍或发生出血；复发指有效治疗后血小板再次<30×10⁹/L、低于基线或出现出血；亦包括停用TPO激动剂后难以维持疗效。 5. 骨髓检查显示巨核细胞增多或正常。 6. 重要器官基本功能正常：超声心动图LVEF≥50%，心电图无显著异常；Cockcroft-Gault公式计算的肌酐清除率≥30 mL/min；ALT/AST≤ULN的3倍；总胆红素和碱性磷酸酶≤ULN的2倍（Gilbert综合征患者≤3倍）；ALC≥0.5×10⁹/L、ANC≥1×10⁹/L、血红蛋白≥60 g/L、血小板≥10×10⁹/L；血氧>92%；ECOG≤2分。 7. 男性及有生育能力女性同意从签署知情同意书至研究药物使用后1年有效避孕。女性筛选及输注前血妊娠试验阴性且非哺乳期。 排除标准： 1. 血小板减少由骨髓增生异常综合征、早期/非典型再生障碍性贫血、血栓性血小板减少性紫癜等引起。 2. 筛选期间骨髓纤维化≥MF-2级（Thieleja 2005欧洲共识评分），或骨髓存在ITP以外可导致血小板减少的原发疾病。 3. 对研究治疗药物任何成分有超敏反应史。 4. 重大器官疾病：NYHAⅢ–Ⅳ级心力衰竭；过去6个月内心肌梗死、冠状动脉旁路移植术或支架置入；室性心律失常或不明原因晕厥（血管迷走性/脱水所致除外）；严重非缺血性心肌病。 5. 筛选前3年内有恶性肿瘤，已根治且入组前至少3年无活动性疾病者，或无疾病证据的充分治疗后非黑色素瘤皮肤癌除外。 6. 过去6个月内有症状性深静脉血栓或肺栓塞，或目前需要抗凝治疗。 7. 筛选前1个月内参加其他干预性临床研究。 8. 筛选前4周内接种活减毒疫苗。 9. 签署知情同意书前6个月内卒中或癫痫（陈旧性腔隙性脑梗死除外）。 10. 乙肝表面抗原或核心抗体阳性且HBV DNA高于正常范围；HCV抗体阳性且外周血HCV RNA高于正常范围；HIV抗体阳性或梅毒检测阳性。 11. 已知骨髓干细胞疾病史。 12. 研究者认为不适合参加研究的其他情况。
Inclusion Criteria: * 1\. Age≥ 18 years old, regardless of gender. 2. Clinical diagnosis of primary immune thrombocytopenia for at least 6 months, platelet count \< 30×10\^9/L within 48 hours before participating in the study. 3\. Positive anti-platelet glycoprotein autoantibodies (such as GPIIb/IIIa). 4. Prior second-line ITP therapy (first-line treatment includes: corticosteroids or immunoglobulins; Second-line therapies include thrombopoietin receptor agonists (eg, eltrombopag, romiplostim) and/or rituximab, but are ineffective (platelet count \< 30×10\^9/L after treatment, or platelet count does not increase twice as much as baseline, or there is bleeding), or relapse after effective treatment (platelet count falls below 30×109/L after effective treatment, or falls below baseline, or bleeding symptoms) or is difficult to maintain after discontinuation of TPO agonists. 5\. Bone marrow examination shows megakaryocytosis or normal. 6. Basic normal functions of important organs:Echocardiography shows an ejection fraction of ≥50% and no significant abnormalities on ECG.Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥ 30 mL/min.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN).Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤ 2.0× ULN (Gilbert's syndrome ≤3.0×ULN).Absolute lymphocyte count (ALC) ≥ 0.5×10\^9/L; Absolute neutrophil count (ANC) ≥1×10\^9/L; Hemoglobin (Hb) ≥ 60 g/L; Platelet count ≥ 10×10\^9/L.Oxygen saturation \> 92%.ECOG performance status ≤2 7. Males and women of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 1 year after the use of the study drug. Women of childbearing potential must have a negative blood pregnancy test at screening and prior to drug infusion and must not be breastfeeding. Exclusion Criteria: * 1\. Thrombocytopenia caused by myelodysplastic syndrome, early aplastic anemia, atypical aplastic anemia, thrombotic thrombocytopenic purpura, etc. 2\. During the screening period, bone marrow examination showed myelofibrosis MF≥2 (European consensus scoring standard Thieleja 2005) or bone marrow examination showed the presence of a primary disease other than ITP that can lead to thrombocytopenia. 3\. History of hypersensitivity to any component of the therapeutic medication. 4. Major organs: NYHA class III to IV congestive heart failure. Myocardial infarction or coronary artery bypass grafting (CABG) or coronary artery stent implantation within 6 months. Ventricular arrhythmias, or history of unexplained syncope (excluding vasovagal syncope or dehydration). History of severe non-ischemic cardiomyopathy. 5\. Malignant disease within 3 years prior to screening, except for the following: malignant disease that has been curatively treated before enrollment and has no known active disease for 3 years ≥; or well-treated non-melanoma skin cancer with no evidence of disease. 6\. Symptomatic deep vein thrombosis or pulmonary embolism within the past 6 months or currently requiring anticoagulation. 7\. Participated in other interventional clinical studies within 1 month prior to screening. 8\. Vaccination of live attenuated vaccine within 4 weeks prior to screening. 9. Stroke or seizure within 6 months prior to signing the ICF (excluding old lacunar cerebral infarction). 10\. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer test exceeds the normal range; Hepatitis C virus (HCV) antibody is positive and the hepatitis C virus (HCV) RNA titer in peripheral blood exceeds the normal range; positive for human immunodeficiency virus (HIV) antibodies; Positive syphilis test. 11\. Known history of bone marrow stem cell disease 12. Other conditions that the investigators consider unsuitable to participate in the study.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：1. Adverse events · Total number, incidence and severity of adverse events (AEs) in patients of LCAR1901 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 · up to 1 years
次要终点：2. The persistence of CAR gene vector injection；Overall remission rate
通过静脉输注抗CD19/BCMA CAR基因载体注射液。
本开放标签、单中心剂量递增研究旨在评估抗CD19/BCMA CAR基因载体注射治疗复发/难治性免疫性血小板减少症患者的安全性和疗效，计划入组最多18人。
This is an open label, single-site, dose-escalation study in up to 18 participants with treatment of relapsed and refractory immune thrombocytopenia. This study aims to evaluate the safety and efficacy of the treatment with an Anti- CD19/BCMA CAR gene vector injection
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