肿瘤细胞治疗研究
英文原题：CD19-CD22-Bispecific Chimeric Antigen Receptor (CAR) T Cell Therapy for Pediatric Patients With Acute Lymphoblastic Leukemia
这是一项 I 期注册临床试验，评估 CD19CAR-T 细胞治疗急性淋巴细胞白血病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 30 例。试验地点：美国 · 孟菲斯（共 1 个中心）。登记号：NCT06777979。
不限性别 · ≤ 21 Years
细胞采集及制备资格 纳入标准： * 年龄<21岁； * 复发/难治性CD19和/或CD22阳性急性白血病，定义为：在接受任何CD19或CD22靶向治疗后2个月内确认CD19和/或CD22阳性；第二次或以上复发；异基因造血干细胞移植（HCT）后任何复发；或旨在诱导缓解的治疗仍不能控制的原发/复发难治性疾病； * 预期生存期>12周； * Karnofsky或Lansky（按年龄选择）评分≥50； * 有生育能力的女性：无哺乳且无哺乳意愿；非妊娠，入组前7天内血清或尿液妊娠检测阴性。 排除标准： * 已知原发性免疫缺陷； * 已知HIV阳性； * 已知有方案规定的淋巴清除化疗禁忌证； * 对含鼠源蛋白制品有超敏反应史。 治疗资格 纳入标准： * 年龄<21岁； * 骨髓中可检测到疾病； * 预期生存期>8周； * Karnofsky或Lansky（按年龄选择）评分>50； * 心功能充分：左心室射血分数>40%或短轴缩短率>25%； * 心电图未见有临床意义的心律失常； * 肾功能充分：肌酐清除率或放射性核素GFR>50 mL/min/1.73 m²；年龄<2岁者GFR>40 mL/min/1.73 m²； * 肺功能充分：用力肺活量（FVC）>预计值的50%，或室内空气下脉搏血氧饱和度>92%； * 总胆红素<该年龄正常值上限的3倍，Gilbert综合征患者除外； * ALT或AST<该年龄正常值上限的5倍； * 既往治疗导致的所有NCI CTCAE III–IV级非血液学急性毒性均已恢复； * 既往接受异基因HCT者，在计划CAR-T输注前须距移植至少3个月、无急性GVHD证据，且计划输注前28天内未接受供者淋巴细胞输注（DLI）； * 有生育能力的女性：无哺乳且无哺乳意愿；非妊娠，入组前7天内血清或尿液妊娠检测阴性；如有性生活，同意避孕至T细胞输注后3个月，男性伴侣应使用避孕套。 排除标准： * 已知原发性免疫缺陷； * 已知HIV阳性； * 已知有方案规定的淋巴清除化疗禁忌证； * 对含鼠源蛋白制品有超敏反应史； * 严重且未控制的细菌、病毒或真菌感染； * 活动性CNS-3级疾病； * 有活动性且未控制的神经系统疾病证据。
Collection and Manufacturing Eligibility Inclusion Criteria: * Age \<21 years old * Relapsed/refractory CD19- and/or CD22-positive acute leukemia defined as: \*CD19 and/or CD22-positivity confirmed within 2 months and after receipt of any CD19 or CD22-directed therapy * Second or greater relapse * Any relapse after allogeneic HCT * Refractory disease (primary or in relapse) despite therapy designed to induce remission * Estimated life expectancy of \> 12 weeks * Karnofsky or Lansky (age-dependent) performance score ≥50 (Appendix A) * For females of childbearing age: * Not lactating with intent to breastfeed * Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment Exclusion Criteria: * Known primary immunodeficiency * Known HIV positivity * Known contraindication to receiving protocol defined lymphodepleting * chemotherapy regimen * History of hypersensitivity reaction to murine protein-containing products Treatment Eligibility Inclusion Criteria: * Age \< 21 years old * Detectable disease in the bone marrow * Estimated life expectancy of \> 8 weeks * Karnofsky or Lansky (age-dependent) performance score \> 50 (Appendix A) * Adequate cardiac function defined as left ventricular ejection fraction \>40%, or shortening fraction \> 25% * EKG without evidence of clinically significant arrhythmia * Adequate renal function defined as creatinine clearance or radioisotope GFR \>50 mL/min/1.73m2 (GFR \>40 mL/min/1.73m2 if \<2 years of age) * Adequate pulmonary function defined as forced vital capacity (FVC) \>50% of predicted value; or pulse oximetry \>92% on room air * Total bilirubin \< 3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5 times the upper limit of normal for age * Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy * Prior to planned CAR T cell infusion, patients with a history of prior allogeneicHCT must be at least 3 months from HCT, have no evidence of acute GVHD, and have not received a donor lymphocyte infusion (DLI) within the 28 daysprior to planned infusion * For females of childbearing age: * Not lactating with intent to breastfeed * Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment * If sexually active, agreement to use birth control until 3 months after T cell infusion. Male partners should use a condom. Exclusion Criteria: * Known primary immunodeficiency * Known HIV positivity * Known contraindication to receiving protocol defined lymphodepleting * chemotherapy regimen * History of hypersensitivity reactions to murine protein-containing products * Severe, uncontrolled bacterial, viral or fungal infection * Active CNS-3 disease * Evidence of active, uncontrolled neurologic disease
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：Recommended phase 2 dose (RP2D) of CD19-CD22-CAR T cells · Phase I design to determine the RP2D of CD19-CD22-CAR T cells. Two (2) dose levels will be evaluated (1x106 and 3x106cells/kg). · up to 4 weeks after CD19-CD22-CAR T-cell infusion；Incidence of adverse events · Will be assessed and graded using the CTCAE v5.0, with the exception of CRS and ICANS, which will be graded according to ASTCT Consensus Guidelines. Adverse events will be summarized descriptively and dose limiting toxicity (DLT) rate will be reported. · up to 4 weeks after CD19-CD22-CAR T-cell infusion
研究分两个阶段：细胞采集和制备阶段，患者在圣犹达血液捐献中心通过单采采集白细胞，或使用医生此前采集并冷冻保存的产品；采集细胞经工程改造以增强识别和杀伤癌细胞的能力，最终产品称为CD19-CD22 CAR-T细胞。治疗阶段，符合条件的患者在接受CAR-T细胞前先进行化疗。
这是一项I期研究，旨在评估CD19-CD22双特异性CAR-T细胞的安全性。主要目标是确定自体CD19-CD22 CAR-T细胞用于≤21岁复发/难治性CD19和/或CD22阳性白血病患者的安全性特征并提出II期推荐剂量（RP2D）；次要目标为评估其抗白血病活性。
This study is a phase I study designed to evaluate the safety of CD19-CD22-CAR T cells. Primary Objective: To determine the safety profile and propose the recommended phase 2 dose (RP2D) of autologous CD19-CD22-CAR T cells in patients ≤ 21 years of age with recurrent/refractory CD19- and/or CD22-positive leukemia. Secondary Objective: To evaluate the anti-leukemic activity of CD19-CD22-CAR T cells.
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