肿瘤细胞治疗研究
英文原题：A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma
这是一项 I 期注册临床试验，评估细胞治疗用于骨肉瘤的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 21 例。试验地点：美国 · 西雅图（共 1 个中心）。登记号：NCT05312411。
不限性别 · ≥ 15 Years 且 ≤ 30 Years
纳入标准： * 难治性或复发/进展性骨肉瘤，按NCCN或儿童肿瘤协作组（COG）临床试验一线治疗失败且无法手术切除，符合以下任一项： 1. 影像学或组织学证实出现新的可测量病灶。 2. 影像学（包括FDG-PET）或组织学证实出现新的可评估病灶。 3. CT/MRI记录至少一个肿瘤维度增加>20%，且既有病灶最长径绝对增加最多5 mm（可包括既往照射病灶）。 4. 持续存在可测量疾病或FDG-PET高摄取骨转移，且对初始常规治疗（手术、放疗和/或化疗）未达到完全缓解。 * 能耐受单采（必要时包括临时单采导管置入），或已有可用于制备的单采产品。 * 预期生存期≥8周。 * Lansky或Karnofsky评分≥50。 * 抗癌药、放疗、细胞毒性化疗、生物治疗、抗肿瘤抗体治疗、基因修饰细胞治疗，以及在无现成单采产品时使用的皮质类固醇（生理替代治疗除外），均已按方案规定的洗脱期停用。 * 血液学、肾、肝、心脏和呼吸功能充分。 * 3个月内HIV、乙肝和丙肝检测阴性。 * 有生育/受孕能力者愿意从治疗期间至研究药物末次输注后12个月使用高效避孕措施。 排除标准： * 除原发恶性实体瘤外存在其他活动性恶性肿瘤；允许存在CNS颅内转移。 * 有症状且需医疗干预的持续CNS病变。 * 正在接受体外放射治疗。 * 存在活动性严重感染。 * 原发性免疫缺陷综合征。 * 妊娠或哺乳期。 * 不愿签署研究参与同意/赞同书，包括15年随访同意。 * 研究者认为会妨碍受试者按本方案接受治疗的任何情况。
Inclusion Criteria: * Refractory or recurrent/progressive osteosarcoma that has failed first line therapy for Osteosarcoma per NCCN or upfront Children's Oncology Group clinical trial and is not amenable to surgical resection (must meet one of the following): 1. New site of measurable disease by radiographic imaging or histologic confirmation 2. New site of evaluable disease by radiographic imaging (including FDG-PET) or histologic confirmation 3. Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a maximum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included) 4. Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy and/or chemotherapy) * Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing * Life expectancy ≥ 8 weeks * Lansky or Karnofsky score ≥ 50 * Anti-cancer agents, radiotherapy, cytoxic chemotherapy, biologic therapy, anti-tumor antibody therapy, genetically modified cell therapy, and, if no apheresis product available, corticosteroid therapy (excluding physiologic replacement), discontinued within protocol specified wash-out period * Adequate hematologic, renal, hepatic, cardiac, and respiratory function. * Negative HIV, hepatitis B and C test within 3 months * If of child-bearing or fathering potential, willing to use highly effective contraception through 12 months following final stud drug infusion Exclusion Criteria: * Active malignancy other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed) * Ongoing, symptomatic CNS pathology requiring medical intervention * Receiving external beam radiotherapy * Presence of active, severe infection * Primary immunodeficiency syndrome * Pregnant or breast feeding * Unwilling to provide consent/assent for study participation, including 15 year follow up * Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.
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：Adverse events associated with ex-vivo expanded autologous T cells genetically modified to express an antiFL(FITC-E2) CAR administered with UB-TT170 will be assessed · The type, frequency, severity, and duration of adverse events will be summarized · 30 days
次要终点：Ability to manufacture antiFL(FITC-E2) CAR cells；Evaluate the pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells
CAR-T细胞给药后，受试者在2周内先接受UB-TT170的3次递增剂量，随后按固定剂量每周给药2周。符合条件者可进入第2–4疗程，每疗程包括每周给予UB-TT170共7次。
本研究旨在了解一种新疗法能否帮助治疗难治性或复发性骨肉瘤患者。研究联合使用UB-TT170和基因修饰的嵌合抗原受体T细胞（CAR-T细胞），其作用机制不同于化疗。研究者通过单采采集患者血液中的T细胞，在实验室将其改造成可识别UB-TT170标记的CAR-T细胞。当扩增出足量抗叶酸荧光素（FITC-E2）CAR-T细胞后，患者可能先接受化疗为新细胞腾出空间，再回输CAR-T细胞。输注CAR-T细胞数天后，患者开始接受叶酸-荧光素UB-TT170输注，剂量在前几次逐渐增加至最大剂量，之后按固定方案给药。UB-TT170可结合肿瘤细胞并对其进行标记，吸引CAR-T细胞前来识别并杀伤肿瘤细胞。研究治疗期约8个月；接受CAR-T细胞输注者须进行15年长期随访。
The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes back after treatment (is recurrent).This study is testing a combination of study therapies, UB-TT170 and genetically modified chimeric antigen receptor T lymphocyte (CAR T) cells, which work together in a way that is different from chemotherapy. In this study, researchers will take some of your blood and remove the T cells in a process called "apheresis". Then the T cells are taken to a lab and changed to CAR T cells that recognize the flags from UB-TT170. Once researchers think they have grown enough CAR T cells, called antiFL(FITC-E2) CAR T cells, to fight your cancer, you may get some chemotherapy to make room in your body for the new cells and then have those cells put back in your body. A few days after the you get your CAR T cell infusion you will start to get infusions of UB-TT170, with the dose slowly increasing for the first few infusions until you have reached a maximum dose that you will get on a regular schedule. The UB-TT170 will attach to your tumor cells and flag them so that they attract the CAR T cells. When the CAR T cells see the labeled tumor cells they can kill the tumor cells. The active part of the study lasts about 8 months, and if you get the CAR T cell infusion you will be in long-term follow-up for 15 years.
MEMBER ACCOUNT
登录成功会直接打开下一页。
