肿瘤细胞治疗研究
英文原题：Allogenic Adipose-Derived Mesenchymal Stem Cells for the Treatment of Recurrent Glioblastoma or Recurrent Astrocytoma in Patients Undergoing Craniotomy
这是一项 I 期注册临床试验，评估异体脂肪间充质干细胞治疗胶质母细胞瘤、胶质瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 20 例。试验地点：美国 · 杰克逊维尔（共 1 个中心）。登记号：NCT05789394。
不限性别 · ≥ 18 Years
纳入标准： * 年龄≥18岁； * Karnofsky体能状态（KPS）≥60； * 仅对有生育能力者：登记前≤7天完成妊娠试验且结果阴性； * 既往组织学诊断为胶质母细胞瘤（异柠檬酸脱氢酶IDH野生型）或星形细胞瘤（IDH突变型，按2021年WHO中枢神经系统肿瘤分类为Ⅳ级），且适合并将接受再次开颅切除复发肿瘤； * 按神经肿瘤免疫治疗反应评估（iRANO）标准存在可测量疾病； * 登记前≤3周血清肌酐和尿素≤正常值上限（ULN）的2倍； * 登记前≤3周ALT、AST和碱性磷酸酶≤ULN的3倍，胆红素≤2.5 mg/dL； * 登记前≤3周凝血酶原时间≤ULN的1.5倍； * 登记前≤3周INR和PTT≤ULN的1.5倍； * 登记前≤3周血红蛋白≥9 g/dL； * 登记前≤3周血小板≥100×10⁹/L； * 登记前≤3周中性粒细胞绝对计数（ANC）≥1.5×10⁹/L； * 愿意在研究主动监测阶段返回入组机构随访； * 患者或法定授权代表能够充分理解方案并提供书面和口头同意； * 愿意提供研究相关性分析所需的血液和组织样本； * 愿意接受Ommaya储液囊置入并提供研究相关脑脊液（CSF）样本。 排除标准： * 仅接受针吸活检或不适合手术； * 肿瘤仅位于脑干、中脑或丘脑，未累及周围脑组织； * 既往接受贝伐珠单抗治疗； * 影像学提示软脑膜疾病。
Inclusion Criteria: * Participants \>= 18 years * Karnofsky Performance Scale (KPS) \>= 60 * Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only * Patients with a previous histological diagnosis of glioblastoma multiforme, isocitrate dehydrogenase (IDH) wildtype (WT) or astrocytoma, IDH-mutant World Health Organization (WHO) grade IV according to the 2021 WHO classification of tumors of the central nervous system , who are candidates to- and will undergo a redo craniotomy for excision of recurrent tumor * There is measurable disease according to the immunotherapy response assessment in neuro-oncology (iRANO) criteria * Serum creatinine and urea \<= 2 times the upper limit of normal (=\< 3 weeks prior to registration) * Alanine transaminase (ALT), aspartate transferase (AST) and alkaline phosphatase =\< 3 times the upper limit of normal, and bilirubin =\< 2.5 mg/dL (=\< 3 weeks prior to registration) * Prothrombin time =\< 1.5 times upper limit of normal (=\< 3 weeks prior to registration) * International normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 times the upper limit of normal (=\< 3 weeks prior to registration) * Hemoglobin \>= 9 g/dL (=\< 3 weeks prior to registration) * Platelets \>= 100 x 10\^9/L (=\< 3 weeks prior to registration) * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (=\< 3 weeks prior to registration) * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Patient or legally authorized representative (LAR) is able to fully understand and provide written and verbal consent for the protocol * Willingness to provide mandatory blood specimens for correlative research * Willingness to provide mandatory tissue specimens for correlative research * Willingness to undergo Ommaya reservoir placement and provide cerebrospinal fluid (CSF) samples for correlative research Exclusion Criteria: * Patients who are undergoing needle biopsy only or non-eligible for a surgical intervention * Tumors located solely in the brain stem, midbrain, or thalamus without inclusion/involvement of surrounding brain matter * Previous treatment with bevacizumab * Radiographic evidence of leptomeningeal disease
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：Maximum tolerated dose (MTD) · Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients). Will use the standard cohort 3+3 design. · Up to 4 weeks
次要终点：Incidence of adverse events (AEs)；Best response；Response rate (RR)；Progression free survival；Overall survival
患者接受鞘内AMSC治疗，并在研究期间开颅手术时置入Ommaya储液囊。研究期间及随访中接受MRI检查，并采集血液、组织和脑脊液样本。
本Ⅰ期试验评估异体脂肪来源间充质干细胞（AMSC）治疗复发性胶质母细胞瘤或星形细胞瘤患者的安全性、副作用及最佳剂量；患者需接受脑部开颅手术。胶质母细胞瘤是最常见且侵袭性最强的原发性恶性脑肿瘤。当前标准治疗包括手术切除，之后接受放疗、化疗及肿瘤电场治疗；尽管采取强化治疗，患者完成治疗后的生存率仍较低，疾病常复发。复发性胶质母细胞瘤可选治疗有限，且对生存改善不明显。AMSC存在于脂肪组织中，从脂肪分离后可在手术时注入手术腔。AMSC与肿瘤细胞直接接触时，可能影响肿瘤生长、残余肿瘤细胞死亡和化疗耐药。开颅手术时将AMSC局部注入复发性胶质母细胞瘤切除腔，可能通过降低恶性细胞进展率和侵袭性，改善患者长期结局。
This phase I trial tests the safety, side effects, and best dose of allogenic adipose-derived mesenchymal stem cells (AMSCs) in treating patients with glioblastoma or astrocytoma that has come back (recurrent) who are undergoing brain surgery (craniotomy). Glioblastoma is the most common and most aggressive form of primary and malignant tumor of the brain. Currently, the standard of care for this disease includes surgical resection, followed by radiation with chemotherapy and tumor treating fields. Despite this aggressive therapy, the survival after finishing treatment remains low and the disease often reoccurs. Unfortunately, the available therapy options for recurrent glioblastoma are minimal and do not have a great effect on survival. AMSCs are found in body fat and when separated from the fat, are delivered into the surgical cavity at the time of surgery. When in direct contact with tumor cells, AMSCs affect tumor growth, residual tumor cell death, and chemotherapy resistance. The use of AMSCs delivered locally into the surgical cavity of recurrent glioblastoma during a craniotomy could improve the long-term outcomes of these patients by decreasing the progression rate and invasiveness of malignant cells.
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