肿瘤细胞治疗研究
英文原题：Brain Tumor-Specific Immune Cells (IL13Ralpha2-CAR T Cells) for the Treatment of Leptomeningeal Glioblastoma, Ependymoma, or Medulloblastoma
这是一项 I 期注册临床试验，评估自体 CAR-T 细胞治疗胶质母细胞瘤、脑肿瘤、肿瘤的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 10 例。试验地点：美国 · 杜阿尔特（共 1 个中心）。登记号：NCT04661384。
不限性别 · ≥ 18 Years
纳入标准： * 已证实存在脑膜转移。 * Karnofsky体能状态评分（KPS）≥60。 * 预期生存期≥8周。 * 如有脑室腹腔分流装置（VP分流），其阀门须可调节，且患者能够耐受关闭分流48小时。 * IL13Rα2-CAR T细胞对胎儿发育的影响尚不明确。因此，有生育能力的女性须血清妊娠试验阴性，并同意在入组前及研究治疗后至少2个月使用可靠避孕方式；男性受试者须同意在研究期间及研究治疗后至少2个月使用可靠避孕方式，且不捐献精子。 * 初诊或复发肿瘤经组织学证实表达IL13Rα2阳性，免疫组织化学（IHC）H评分≥50。 * 能理解研究内容并愿意签署书面知情同意书。 * 无白细胞单采、类固醇或托珠单抗的已知禁忌证。 排除标准： * 需补充氧气才能维持血氧饱和度>95%，且预计2周内无法缓解。 * 需接受透析。 * 癫痫发作未控制和/或存在临床可见的进行性脑病。 * 无法理解本Ⅰ期研究的基本内容和/或参加研究的风险与获益；可由法定监护人代为理解并作出决定。 * 不愿在IL13Rα2-CAR T细胞研究首4个周期开始前1周及治疗期间停止化疗、内分泌治疗和/或放疗。 * 使用分流装置者，其阀门不可调节，或不能耐受关闭分流48小时。 * 存在凝血障碍或出血性疾病，或无法在置入Rickham储液囊前安全停用抗凝药。 * 存在慢性或活动性CNS病毒感染。 * 有任何未控制疾病，包括持续或活动性感染；已知活动性乙肝或丙肝感染；或存在活动性感染体征/症状、血培养阳性或影像学感染证据。 * 在签署主要知情同意书前4周内检测为HIV血清阳性。 * 患有自身免疫性疾病。 * 存在其他活动性恶性肿瘤。 * 无法接受脑部磁共振成像（MRI）。 * 妊娠或哺乳期。母亲接受IL13Rα2-CAR T细胞治疗后，哺乳婴儿可能存在未知但潜在的不良事件风险；如母亲希望参加本研究，须停止哺乳。 * 研究者认为可能无法遵守全部研究程序（包括可行性/后勤方面的依从性问题）。
Inclusion Criteria: * Participant has verified leptomeningeal metastases * Participant must have a Karnofsky performance status (KPS) \>= 60 * Participant must have a life expectancy of \>= 8 weeks * If participant has a ventriculoperitoneal shunt, the valve must be programmable, and must be able to tolerate their shunts being turned off for 48 hours * The effects of IL13Ralpha2-CAR T cells on a developing fetus are unknown. For this reason, women of child-bearing potential must have negative serum pregnancy test and agree to use a reliable form of birth control prior to study entry and for at least two months following study treatment. Male research participants must agree to use a reliable form of birth control and not donate sperm during the study and for at least two months following study treatment * Participant has a histologically confirmed IL13Ralpha2+ tumor expression by immunohistochemistry (IHC) at the initial tumor presentation or recurrent disease (H-score \>= 50) * Participant must have the ability to understand and the willingness to sign a written informed consent * No known contraindications to leukapheresis, steroids, or tocilizumab Exclusion Criteria: * Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks * Research participant requires dialysis * Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy * Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase 1 study. A legal guardian may substitute for the research participant * Participant is unwilling to stop treatment with chemotherapy or endocrine therapy and/or radiation one week prior and during the first 4 cycles of the IL13Ralpha2-CAR T cell study * Shunted participants either have a non-programmable shunt valve, or cannot tolerate their shunts being turned off for 48 hours * Participant has a coagulopathy or bleeding disorder or cannot safely discontinue anticoagulation prior to placement of a Rickham reservoir * Participant has a chronic or active viral infection of the central nervous system (CNS) * Participant has any uncontrolled illness, including ongoing or active infection; participant has known active hepatitis B or C infection; participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections * Participant is human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of signing the main informed consent * Participant has an autoimmune disease * Participant has another active malignancy * Participant is unable to undergo a brain magnetic resonance imaging (MRI) * Participant is pregnant or breast feeding. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IL13Ralpha2-CAR T cells, breastfeeding should be discontinued if the mother wants to participate in this study * Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
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：Incidence of adverse events · Will be assessed using the NCI's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. · Up to 15 years；Overall survival · The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. · At 3 months
次要终点：CAR T cell detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)；Endogenous T cell levels detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)；Cell phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF)；Cytokine levels in PB, TCF and CSF；Disease response；Time to progression；Overall survival；CAR T and endogenous cells detected in tumor tissue
患者于第1天通过脑室内给药（ICV）在5分钟内输注IL13Rα2-CAR T细胞；如无疾病进展或不可接受的毒性，每7天重复一次，共4个周期。
本Ⅰ期试验评估脑肿瘤特异性免疫细胞（IL13Rα2-CAR T细胞）治疗胶质母细胞瘤、室管膜瘤或髓母细胞瘤脑膜播散患者的副作用。免疫细胞是免疫系统的一部分，可帮助机体抵御感染和其他疾病，也可在实验室中经工程改造以杀伤脑肿瘤细胞。IL13Rα2-CAR T细胞具有脑肿瘤靶向性，可将其基因导入并表达于免疫细胞中；用于脑膜播散患者时，可能帮助免疫细胞更好地识别并杀伤肿瘤细胞。
This phase I trial investigates the side effects of brain tumor-specific immune cells (IL13Ralpha2-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma, ependymoma, or medulloblastoma. Immune cells are part of the immune system and help the body fight infections and other diseases. Immune cells can be engineered to destroy brain tumor cells in the laboratory. IL13Ralpha2-CAR T cells is brain tumor specific and can enter and express its genes in immune cells. Giving IL13Ralpha2-CAR T cells may better recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma, ependymoma or medulloblastoma.
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