肿瘤细胞治疗研究
英文原题：Early Phase I Study of Autologous T Cells (EX02 CAR-T) for Unresectable Pancreatic/Bile Duct Cancer
Early Phase I Study of Autologous T Cells (EX02 CAR-T) for Unresectable Pancreatic/Bile Duct Cancer
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⚠ 该试验的登记信息已有 33 个月未更新， 页面上显示的「尚未开始招募」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项早期 I 期注册临床试验，评估 CAR-T 细胞治疗胰腺癌、恶性肿瘤的安全性、可行性及初步疗效。当前状态：尚未开始招募。计划入组 6 例。登记号：NCT06196658。
不限性别 · ≥ 18 Years 且 ≤ 70 Years
纳入标准 1. 确诊不可切除或转移性胰腺癌或胆管癌。 2. 一线或二线化疗不适用、治疗难治或治疗后复发。 3. 按RECIST v1.1至少有一个可测量靶病灶。 4. 肿瘤细胞膜EX02阳性（肿瘤组织免疫组化，或腹水细胞流式细胞术检测）。 5. 男女不限，年龄≥18岁。 6. ECOG体能状态0至1。 7. 预期生存期>3个月。 8. 筛选时及开始淋巴清除化疗或研究药物前妊娠试验阴性；有生育能力女性愿意采取避孕措施。 9. 过去4周未输血或使用生长因子，且血液学功能充分：中性粒细胞≥1.5×10^9/L；血红蛋白≥90 g/L；血小板≥100×10^9/L；淋巴细胞≥0.5×10^9/L。 10. 肝、肾、心、肺功能充分：肌酐清除率≥60 mL/min；ALT、AST≤2.5×ULN（肝脏受累时≤5×ULN）；LVEF≥50%、无心包积液且心电图无显著异常；无胸腔积液或仅少量积液、无腹水或仅少量腹水，血氧饱和度≥95%。 11. 自愿参加试验并签署知情同意书。 排除标准 1. 活动性病毒感染，包括但不限于甲肝、乙肝、丙肝或HIV感染。 2. 获得性免疫缺陷综合征（AIDS）史。 3. 妊娠或哺乳。 4. 不愿采取避孕措施。 5. 计划在28天内接受腹腔化疗（如腹腔热灌注化疗，HIPEC）。 6. 开始预处理化疗前2周内使用全身免疫抑制剂或皮质类固醇（泼尼松≥15 mg/日或等效剂量）。 7. 存在以下任一活动性情况：需全身治疗的感染；活动性凝血障碍或接受抗凝治疗（阿司匹林除外）；活动性溶血性贫血；显著心律失常，或心肌梗死、室性心动过速、心室颤动史；活动性阻塞性或限制性肺病；类风湿关节炎等活动性自身免疫病或免疫缺陷病；活动性CNS转移或脑脊液恶性肿瘤；未控制的心血管、呼吸、肾、胃肠、泌尿生殖或免疫系统疾病。 8. 除研究目标肿瘤外另有活动性恶性肿瘤；低风险肿瘤除外，如非转移性基底细胞或鳞状细胞皮肤癌。 9. 对本研究计划使用的任何药物有超敏反应史。 10. 既往接受过任何基因修饰T细胞治疗（包括CAR-T 或TCR-T）。 11. 研究者认为不适合参加研究的其他情况。 注：登记记录在“排除标准”标题下重复列出全部入选条件，并写有“将入组28名受试者”；上述标准已按其后单独列明的排除条件整理。
Inclusion Criteria:
* 1\) Must have a confirmed diagnosis of unresectable or metastatic pancreatic cancer or bile duct cancer 2) Ineligible for, refractory to or relapsed after first or second line of chemotherapy 3) Presence of at least one measurable target lesion according to RECIST v1.1 4) EX02 positive tumor cell membrane (as shown in IHC staining of tumor specimen or in flow cytometry of ascites cells) 5) Male or female, ≥18 years 6) ECOG performance status 0 to 1 7) Expected life expectancy \>3 months 8) Negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration, and willingness to practice birth control for woman with childbearing potential 9) Adequate hematology function indicated by followings (without blood transfusion or administration with growth factors in last four weeks):
1. Neutrophil count ≥ 1.5×10\^9/L
2. Hemoglobin ≥ 90g/L
3. Platelet count ≥ 100×10\^9/L
4. Lymphocyte count ≥ 0.5×10\^9/L 10) Adequate liver, kidney, heart and lung functions at least indicated by:
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1. Creatinine clearance ≥ 60ml/min
2. ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved)
3. LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam
4. No or only small amount of pleural fluid or ascites; blood oxygen saturation ≥ 95% 11) Voluntary participation in the trial and signing informed consent form
Exclusion Criteria:
* 28 participants fulfilling the following criteria will be enrolled.
Inclusion criteria:
1. Must have a confirmed diagnosis of unresectable or metastatic pancreatic cancer or bile duct cancer
2. Ineligible for, refractory to or relapsed after first or second line of chemotherapy
3. Presence of at least one measurable target lesion according to RECIST v1.1
4. EX02 positive tumor cell membrane (as shown in IHC staining of tumor specimen or in flow cytometry of ascites cells)
5. Male or female, ≥18 years
6. ECOG performance status 0 to 1
7. Expected life expectancy \>3 months
8. Negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration, and willingness to practice birth control for woman with childbearing potential
9. Adequate hematology function indicated by followings (without blood transfusion or administration with growth factors in last four weeks):
1. Neutrophil count ≥ 1.5×10\^9/L
2. Hemoglobin ≥ 90g/L
3. Platelet count ≥ 100×10\^9/L
4. Lymphocyte count ≥ 0.5×10\^9/L
10. Adequate liver, kidney, heart and lung functions at least indicated by:
1. Creatinine clearance ≥ 60ml/min
2. ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved)
3. LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam
4. No or only small amount of pleural fluid or ascites; blood oxygen saturation ≥ 95%
11. Voluntary participation in the trial and signing informed consent form
Exclusion criteria:
1. Active viral infection including but not limiting hepatitis A, hepatitis B, hepatitis C or HIV
2. History of acquired immunodeficiency syndrome (AIDS)
3. Is pregnant or lactating
4. Unwilling to practice birth control
5. Planned intraperitoneal chemotherapy (such as HIPEC) within 28 days
6. Received systemic immune inhibitors or corticosteroids (prednisone 15mg/day or above equivalent dose) within 2 weeks of the time of initiating conditioning chemotherapy
7. Current involvement of:
1. Active infection which requires treatment with systemic administration
2. Active coagulation disorders or receiving anti-coagulant treatment (except for aspirin)
3. Active hemolytic anemia
4. Significant arrhythmia, or history of myocardial infarction, ventricular tachycardia, or ventricular fibrillation
5. Active obstructive or constrictive lung disease
6. Active autoimmune disease such as rheumatoid arthritis or immunodeficiency disease
7. Active CNS metastases or cerebrospinal malignancy
8. Uncontrolled diseases including disorders of cardiovascular, respiratory, renal, gastrointestinal, urogenital or immune systems
8. Active second malignancy in addition to the studied one, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
9. History of hypersensitivity to any drugs planning to be used in this study
10. History of treatment with any genetically modified T cell therapy (including CAR T cells and TCR T cells)
11. Any conditions that investigator consider as ineligibility of participation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：Frequency and severity of treatment-related adverse events (TEAEs) · Grade and type of toxicity per dose level; fraction of patients who experience toxicity (including allergic reactions to T cell infusions) of ≥ Grade 3 according to CTCAEv5.0, cytokine release syndrome (CRS) of ≥ Grade 3 according to ASTCT consensus and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). · 4 weeks after the first CAR-T cell infusion；Objective Response Rate · Objective Response Rate (ORR) is the proportion of participants with an objective response (either a complete response \[CR\] or partial response \[PR\]) in participants who received at least 1 dose of EX02CART and at least the 6-week tumor evaluation as determined by the investigator according to RECIST v1.1. · 24 weeks
次要终点：Progression Free Survival (PFS)；Duration of Response (DOR)；Overall survival (OS)；Disease control rate (DOC)；5) Volume of ascites measured by ultrasonography and/or frequency and volume of ascites aspiration
入组后进行白细胞单采，随后接受环磷酰胺和氟达拉滨预处理化疗，并向肿瘤内注射或腹腔输注EX02 CAR-T 细胞；之后可能再静脉输注EX02 CAR-T 细胞。研究流程包括筛选、入组/白细胞单采、预处理化疗、CAR-T 治疗、治疗后评估及长期随访。
以上邮箱 / 电话是登记库里的申办方联系方式（中国内地座机），通常不直达某家医院。中国中心的联系方式请以医院或登记平台最新公示为准。
这是一项早期I期开放标签研究，探索EX02 CAR-T 细胞治疗不可切除和/或转移性胰腺癌/胆管癌的安全性及潜在疗效。每位受试者入组后进行白细胞单采，接受环磷酰胺和氟达拉滨预处理化疗，并接受EX02 CAR-T 细胞瘤内注射或腹腔输注，之后可能静脉输注。研究流程包括筛选、入组/白细胞单采、预处理化疗、CAR-T 治疗、治疗后评估及长期随访。
This is a early Phase 1 open-label study to explore the safety and possible efficacy of EX02 CAR T cell therapy in the treatment of patients with unresectable and/or metastatic pancreatic/bile duct cancer. Each participant will undergo leukapheresis after enrolment, receive treatment of the conditioning chemotherapy of cyclophosphamide and fludarabine, and an intra-tumoral injection or intraperitoneal infusion of Ex02 CAR T cells, probably followed by an intravenous infusion of EX02 CAR T cells. Each participant will proceed through the following study procedures: * Screening * Enrollment/Leukapheresis * Conditioning chemotherapy * CAR T treatment * Post-treatment assessment * Long-term follow-up
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