肿瘤细胞治疗研究
英文原题：Allogeneic T Cells Expressing T Cell Receptor-KDEL and the Chimeric Antigen Receptor CAT19 for the Treatment of Advanced CD19+ Malignancies
这是一项 I 期注册临床试验，评估 T 细胞治疗恶性肿瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 12 例。试验地点：欧洲 · 伦敦（共 1 个中心）。登记号：NCT05391490。
不限性别 · ≥ 16 Years 且 ≤ 65 Years
纳入标准： 1. 年龄16～65岁。 2. 至少接受过2线治疗后仍复发或难治的B细胞恶性肿瘤： • B-ALL：接受标准治疗后复发或难治，需要挽救治疗，且主管医生认为其他治疗方案不适宜；或 • 大B细胞淋巴瘤（LBCL）：弥漫性大B细胞淋巴瘤（DLBCL，包括滤泡性淋巴瘤转化者，但不包括Richter转化）或原发纵隔大B细胞淋巴瘤（PMBCL）在至少2线治疗后复发／难治；既往治疗须包括利妥昔单抗、蒽环类药物及自体CD19 CAR治疗（无法制备CD19 CAR者除外）；或 • 套细胞淋巴瘤（MCL）：至少2线治疗后复发／难治；既往治疗须包括利妥昔单抗、布鲁顿酪氨酸激酶抑制剂及自体CD19 CAR治疗（无法制备CD19 CAR者除外）；或 • 惰性B细胞非霍奇金淋巴瘤（B-NHL；包括滤泡性淋巴瘤、边缘区淋巴瘤或其他低级别淋巴瘤）：至少2线治疗后复发／难治；既往治疗须包括抗CD20治疗及蒽环类药物或苯达莫司汀化疗。 3. 疾病为CD19阳性。 4. 同意接受妊娠检测并在适用时采取适当避孕措施。 5. 已签署书面知情同意书。 排除标准： 1. CD19阴性疾病。 2. 存在活动性中枢神经系统（CNS）受累。 3. 诊断为慢性淋巴细胞白血病／小淋巴细胞淋巴瘤或伯基特淋巴瘤。 4. 存在活动性乙型肝炎、丙型肝炎或HIV感染。 5. 静息空气下血氧饱和度≤90%。 6. 胆红素>正常值上限的2倍。 7. 肾小球滤过率（GFR）<30 mL/min。 8. 妊娠期或哺乳期女性。 9. 仅适用于造血干细胞移植患者：存在活动性显著急性移植物抗宿主病（GvHD；按改良Glucksberg标准为总体≥Ⅱ级），或需要免疫抑制治疗和／或全身性糖皮质激素治疗的中重度慢性GvHD（按NIH共识标准）。 10. Karnofsky体能状态评分<60%。 11. 已知对白蛋白或二甲基亚砜（DMSO）过敏。 12. 正在接受泼尼松>5 mg/日（或等效剂量）且无法停用糖皮质激素。 13. 预期寿命<3个月。 14. 存在心律失常（控制良好的心房颤动或其他室上性心动过速除外），或显著心脏疾病且左心室射血分数<40%。 15. 能够合理获得作为标准治疗或临床试验组成部分的自体CD19 CAR治疗者。 *此类患者将优先考虑接受自体治疗，而非入组KCAT19研究。
Inclusion Criteria:
1. Age 16-65 years
2. Relapsed or refractory B cell malignancy following at least 2 prior lines of therapy:
B-ALL: relapsed or refractory B-ALL following standard therapy, requiring salvage, in whom alternative therapies are deemed inappropriate by their treating physician Or LBCL: relapsed/refractory DLBCL (incl. transformed FL but not Richter's transformation) or PMBCL following ≥2 prior lines of therapy which must include Rituximab, anthracycline and autologous CD19 CAR, (unless CD19 CAR cannot be manufactured) Or MCL: relapsed/ refractory disease following ≥2 lines of therapy which must include Rituximab, Bruton's tyrosine kinase inhibitor and autologous CD19CAR therapy (unless CD19 CAR cannot be manufactured) Or Indolent B-NHL (either Follicular Lymphoma, Marginal Zone Lymphoma or other low-grade lymphoma) which is relapsed / refractory following ≥2 prior lines of therapy which must include anti-CD20 therapy and chemotherapy with anthracycline or bendamustine.
3. CD19+ disease
4. Agreement to have a pregnancy test, use adequate contraception (if applicable)
5. Written informed consent
Exclusion Criteria:
1. CD19 negative disease
2. Active CNS involvement of disease
3. Diagnosis of chronic lymphocytic leukaemia/ small lymphocytic lymphoma or Burkitt lymphoma
4. Active hepatitis B, C or HIV infection
5. Oxygen saturation ≤ 90% on air
6. Bilirubin \>2 x upper limit of normal
7. GFR \<30ml/min
8. Women who are pregnant or breast feeding
9. Stem Cell Transplant patients only: active significant acute GvHD (overall Grade ≥ II, Modified Glucksberg criteria) or moderate/severe chronic GvHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
10. Karnofsky score \<60%
11. Known allergy to albumin or DMSO
12. Patients receiving corticosteroids at a dose of \>5 mg prednisolone per day (or equivalent) that cannot be discontinued
13. Life expectancy \<3 months
14. Cardiac dysrhythmias (excluding well-controlled AF or other supraventricular tachycardia) or significant cardiac disease and left ventricular ejection fraction \<40%
15. Patients who can reasonably access autologous CD19 CAR treatment as part of standard of care or a clinical trial\*
* These patients will be initially considered for autologous treatment in preference to enrolling on KCAT19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：KCAT 19 T cell generation feasibility · Feasibility of generation of T cell receptor-negative KCAT19 T cells as evaluated by the number of therapeutic products generated. · Up to 28 days after last patient is recruited；KCAT19 T cell Toxicity · Toxicity following KCAT19 T cell administration as evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP · Up to 28 days after last patient treated
次要终点：Response rate；KCAT19 T cell persistence；KCAT19 T cell persistence；Hypogammaglobulinaemia and B cell aplasia；Time to Disease Progression；Event-Free survival；Overall Survival
先进行淋巴细胞清除治疗，随后给予一剂KCAT19 T细胞。
KCAT19是一项单中心、非随机、开放标签的Ⅰ期临床试验，研究一种先进治疗试验用药品（ATIMP），对象为16～65岁的高危、复发／难治性（r/r）B细胞恶性肿瘤成人患者。
KCAT19 is a single-centre, non-randomised, open-label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age 16-65 years) with high risk, relapsed/refractory (r/r) B cell malignancies.
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