肿瘤细胞治疗研究
英文原题："Phase I / II Study on Infusion of Natural Killer Cells After Haploidentical Transplantation in Pediatric Patients"
⚠ 该试验的登记信息已有 18 个月未更新， 页面上显示的「进行中（不再招募）」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 I/II 期注册临床试验，评估 NK 细胞治疗白血病的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 18 例。试验地点：欧洲 · 圣地亚哥-德孔波斯特拉、奥维耶多、巴塞罗那、马德里（共 10 个中心）。登记号：NCT05304754。
不限性别 · ≤ 21 Years
纳入标准： • 年龄≤21岁，男女均可。 • 在所需供者采集时间内无可用HLA完全相合供者（亲属或无关供者），但有单倍型相合供者。 • 确诊高危血液系统恶性肿瘤，包括：高危ALL第一次完全缓解（RC1）；ALL第二次完全缓解（RC2）；ALL第三次或以后完全缓解（RC3+）；高危AML RC1；AML RC2或以后；复发AML且骨髓原始细胞<25%；既往治疗相关AML且CR>12个月；原发或继发骨髓增生异常综合征；NK细胞白血病、双表型或未分化白血病RC1或以后；加速期CML、慢性期但分子检测持续阳性或不耐受TKI；霍奇金淋巴瘤在自体造血祖细胞移植失败后达到RC2或以后，或不能动员造血祖细胞进行自体移植；非霍奇金淋巴瘤在自体移植失败后达到RC2或以后，或不能动员造血祖细胞进行自体移植；幼年型粒-单核细胞白血病。 • 移植前评估符合要求：LVEF>40%或缩短分数≥25%；肌酐清除率（ACr）或GFR≥50 mL/min/1.73m²；FVC≥预计值50%，不能进行肺功能检查者脉搏血氧饱和度≥92%；Karnofsky或按年龄适用的Lansky评分≥50；胆红素≤年龄对应ULN的3倍；ALT≤年龄对应ULN的5倍；女性非哺乳期；入组时无未控制的细菌、真菌或病毒感染。 • 有生育能力女性须在入组前14天内血清或尿妊娠试验阴性，并同意研究期间及末次研究访视后6个月内采用高效避孕方法（如隔膜加杀精剂、避孕套加杀精剂、口服避孕药联合第二种方法、植入剂、注射避孕药、永久性宫内节育器、禁欲或伴侣输精管结扎）。有生育能力男性须承诺研究期间及之后最长6个月使用适当屏障避孕法。 排除标准： • 存在活动性感染或其他严重基础疾病。 • 研究者判断既往治疗依从性差。 • 心理社会评估认为不适合接受该程序，包括家庭/社会状况无法保障正确参与；疾病相关创伤后应激障碍、恐惧症、妄想、精神病等情绪/心理问题且需要专科支持；或家庭成员参与患者健康管理情况不适合。 • 无法理解试验相关信息。 • 治疗开始前30天内或研究药物5个半衰期内（取较长者）接受过研究性药物。
Inclusion Criteria: * Patients of both sexes with age ≤ 21 years. * Not having an identical HLA donor (family or non-family) available in the time needed for the donation of hematopoietic parents. * Having a haploidenic donor available * Diagnosis of high-risk hematological malignancy. This includes: * i. High risk ALL in first complete remission (RC1); * ii. ALL in second complete remission (RC2); * iii. ALL in third complete remission (RC3) or later; * iv. High risk AML in RC1; * v. AML in RC2 or later; * vi. Relapsed AML with \<25% blasts in bone marrow; * vii. AML related to previous treatments in CR\> 12 months; * viii. Primary or secondary myelodysplastic syndrome * ix. NK cell leukemia, biphenotypic or undifferentiated in RC1 or later, * x. Chronic myeloid leukemia (CML) in accelerated phase, in chronic phase with persistent molecular positivity, or with intolerance to tyrosine kinase inhibitors * xi. Hodgkin's lymphoma in RC2 or later after failure of autologous TPH, or unable to mobilize hematopoietic progenitors for autologous TPH * xii. Non-Hodgkin's lymphoma in RC2 or later after failure of autologous TPH, or unable to mobilize hematopoietic progenitors for autologous TPH * xiii. Myelomonocytic juvenile leukemia. * Positive pre-transplant evaluation * i. Left ventricular ejection fraction \> 40% or shortening fraction ≥ 25%; * ii. Creatinine clearance (ACr) or glomerular filtration rate (TFG) ≥ 50 ml/min/1.73 m2 * iii. Forced Vital Capacity (FVC) ≥ 50% of predicted value or pulse-oximetry ≥ 92% if the patient cannot perform the pulmonary function tests; * iv. Karnofsky or Lansky Index (depending on the patient's age) ≥ 50; * v. Bilirubin ≤ 3 times the upper limit of normal for age * vi. Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age * vii. Women who are not breastfeeding. * viii. No uncontrolled bacterial, fungal, or viral infections at the time of inclusion. * Women of childbearing potential must have a negative serum or urine pregnancy test performed within 14 days prior to trial inclusion and must agree to use highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, oral contraceptive combined with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence, or partner with vasectomy) during study participation and for six months after the last trial visit. In the case of male patients with reproductive capacity, they must commit to using an appropriate barrier method for the duration of the study and for up to 6 months thereafter Exclusion Criteria: * Patients with an active infectious process or other serious underlying medical condition * Patients who, according to the investigator's criteria, have a history of poor compliance with therapy. * Patients who after a psycho-social evaluation are advised as not suitable for the procedure: * i. Social-family situation that makes correct participation in the study impossible. * ii. Patients with emotional or psychological problems secondary to the illness such as post-traumatic stress disorder, phobias, delusions, psychosis, with the need for support from specialists. * iii. Evaluation of the involvement of family members in the health of the patient * Inability to understand the information about the trial * Received an investigational drug within 30 days prior to the start of therapy or within 5 half-lives of receiving an investigational drug, whichever is longer.
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：Dose-limiting toxicity (TLD) · To determine dose-limiting toxicity (TLD) of a single infusion of aloreactive NK cells or ex vivo IL-15-stimulated NK cells after haploTPH in pediatric patients with high-risk leukemias. · 52 weeks；Maximum tolerated dose (MTD) · To determine maximum tolerated dose (MTD) of a single infusion of aloreactive NK cells or ex vivo IL-15-stimulated NK cells after haploTPH in pediatric patients with high-risk leukemias. · 52 weeks
次要终点：Efficacy of post haploTPH NK cell therapy；Clinical evolution of patients；Monitor immune reconstitution and characterize NK cells
每个队列中3名患者接受来自KIR不匹配供者的异体反应性NK细胞。
每个队列中3名患者接受来自KIR匹配供者、经IL-15体外刺激的NK细胞。
本I/II期研究评估儿童血液系统恶性肿瘤患者接受单倍型相合造血祖细胞移植后，单次输注异体反应性自然杀伤（NK）细胞或体外经IL-15刺激的NK细胞的安全性和疗效。
Phase I / II study on infusion of alloreactive or stimulated Natural Killer cells with IL-15 ex vivo after haploidentical transplantation of hematopoietic progenitors in pediatric patients with hematologic malignancies (PHINK
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