肿瘤细胞治疗研究
英文原题：Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHL
这是一项 II 期注册临床试验，评估细胞治疗用于非霍奇金淋巴瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 26 例。试验地点：其他 · 安曼（共 1 个中心）。登记号：NCT07271121。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： 1. 侵袭性非霍奇金淋巴瘤，且符合以下之一：至少一种标准化疗及一种挽救治疗方案后进展；计划异基因干细胞移植但被判定不适合；或异基因移植后至少100天复发、无活动性GVHD且入组前至少30天未使用免疫抑制药物。 2. 有CNS疾病者（孤立性CNS淋巴瘤除外），仅当入组时CNS疾病已成功清除方可入组。 3. 流式细胞术或免疫组化证实恶性细胞表达CD19。 4. 年龄>18岁且≤75岁（经治疗研究者判定身体状况适合）。 5. FACS测得基线CD3+ T细胞计数≥100/μL。 6. 筛选时ECOG评分0–2。 7. 无活动性乙肝、丙肝或HIV I/II感染。 8. 无生育能力者可入组；有生育能力女性须在开始淋巴细胞清除化疗前7天内及桥接化疗前妊娠检测阴性。 9. 研究专属程序开始前已签署并注明日期的知情同意书。 排除标准： 1. 有残留CNS疾病。 2. 当前患自身免疫病，或有可能累及CNS的自身免疫病史。 3. 活动性且有临床意义的CNS功能障碍，包括未控制癫痫、脑血管缺血/出血、痴呆或瘫痪等。 4. 有其他恶性肿瘤史，非黑色素瘤皮肤癌或原位癌除外；如已无病≥3年，可考虑入组。 5. 肺功能不足：既往重度肺病、DLCO<50%或影像学显示活动性肺浸润。 6. 心功能不足：超声心动图显示LVEF<50%。 7. 肾功能不足：≥18岁患者按Cockcroft-Gault公式计算肌酐清除率<50 mL/min/1.73 m²。 8. 肝功能异常：血清胆红素≥ULN的3倍，或AST/ALT>ULN的5倍；研究者判断由淋巴瘤肝浸润导致者除外。 9. 研究者认为疾病进展过快，可能影响完成研究治疗。 10. 妊娠或哺乳期女性。 11. 白细胞单采前30天内接受全身化疗、皮质类固醇（生理性替代剂量除外）、氟达拉滨/氯法拉滨、免疫抑制剂（钙调神经磷酸酶抑制剂）、抗体、试验药物、供者淋巴细胞输注或放疗；输注前2周内使用利妥昔单抗。鞘内化疗允许，但须在CART19输注前10天停用以降低神经毒性风险。 12. 有生育能力者不同意从入组至CAR-T给药后3个月采取有效避孕措施。 13. 同时参加可能与本研究相互影响的其他干预性试验（如CAR-T试验）。 14. CART输注前4周内接受其他试验性治疗。 15. 存在脑功能障碍或成年患者无法律行为能力。 16. 因司法或行政命令被收容于机构。
Inclusion Criteria: 1. Eligible patients with a diagnosis of aggressive NHL: 1. Patients after progression on at least one standard chemotherapy and one salvage regimen or 2. Patients considered for alloSCT but are found ineligible or 3. Patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. 2. Patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared at the time of inclusion. 3. CD19 expression must be detected on the malignant cells by flow cytometry or immunohistochemistry 4. Age \> 18 year up to 75 years old (if deemed fit by treating investigator); 5. Baseline absolute CD3+ T cell count by FACS ≥100/µl; 6. ECOG performance score of 0-2 at screening; 7. No active Hepatitis B, Hepatitis C, HIV I/II 8. No childbearing potential or negative pregnancy test at screening within 7 days from starting lymphodepletion chemotherapy and before bridging chemotherapy in women with childbearing potential; 9. Signed and dated informed consent, before conduct of any trial-specific procedure. Exclusion Criteria: 1. Residual CNS disease 2. Current autoimmune disease, or history of autoimmune disease with potential CNS involvement; 3. Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis) 4. History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years; 5. Pulmonary function: Patients with pre-existing severe lung disease or DLCO of less than 50% or active pulmonary infiltrates on imaging studies. 6. Cardiac function: left ventricular ejection faction \<50% by echocardiogram, 7. Renal function: Creatinine clearance \<50 mL/min/1.73 m2, by Cockcroft-Gault formula (Cockcroft and Gault 1976) for patients ≥18 years. 8. Liver function: patients with serum bilirubin ≥3 times upper limit of or AST or ALT \> 5 times upper limit of normal, unless due to lymphoma liver infiltration in the estimation of the investigator. 9. Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy; 10. Pregnant or breast-feeding females 11. Medications: systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, Fludarabine/clofarabine or immunosuppressive (Calcineurin inhibitors) drugs and antibodies or investigational drugs or donor lymphocyte transfusions or radiation therapy within 30 days prior to apheresis, and rituximab within 2 weeks with the exception of Intrathecal chemotherapy is allowed prior to treatment, but should be discontinued 10 days prior to-CART19 infusion to limit the risk of neurotoxicities; 12. Patients of child-bearing or fathering potential not willing to practice an effective form of birth control from the time of enrollment and for three months after dosing of the CARTs; 13. Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials. 14. Other investigational treatment within 4 weeks before CARTs infusion; 15. Cerebral dysfunction, legal incapacity of adult patients; 16. Committal to an institution on judicial or official order.
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：overall response rate · ORR in NHL patients defined as the rate of overall response (CR or PR) · on week 4 and at month 3 in patients not achieving CR on week 4
次要终点：Safety and toxicity；CRS；Disease-free survival；Duration of response；ICANS；relapse rate；time to relapse；overall survival
患者单次接受新鲜MB-CART-19.1输注，剂量水平1为3×10⁶个细胞/kg（按实际体重）。白细胞单采所得产品使用自动化封闭式CliniMACS Prodigy系统为患者个体化制备MB-CART19.1。
这是一项前瞻性、单中心、开放标签、非随机、单臂、单次给药Ⅱ期临床试验。符合入选标准的CD19阳性非霍奇金淋巴瘤成人患者接受单次新鲜MB-CART-19.1输注，随后随访12个月以评估疗效和安全性。
This is a Prospective Single Center, open label, Non-randomized, Single Arm, Single Dose, Phase II Clinical Trial. Adult patients \>18-year-old with CD19+ Non-Hodgkin lymphoma are eligible for the study if they meet eligibility criteria. Patients will receive a fresh single dose of MB-CART-19.1 and will be followed for 12 months and evaluated for efficacy and safety.
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