肿瘤细胞治疗研究
英文原题：NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
这是一项 I 期注册临床试验，评估细胞治疗用于淋巴瘤、急性淋巴细胞白血病、大 B 细胞淋巴瘤的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 150 例。试验地点：美国 · 丹佛、克利夫兰、坎珀当、悉尼（共 6 个中心）。登记号：NCT05020678。
不限性别 · ≥ 18 Years
纳入标准： 一般要求：ECOG体能状态评分≤1分。 疾病相关条件： * 按WHO 2016分类，组织学或细胞学确诊复发/难治性B细胞NHL、CLL或B-ALL； * 既往接受CD19/CD20靶向治疗者，疾病仍须分别保持CD19和/或CD20阳性； * 有可测量疾病； * 既往接受≥2线治疗；但套细胞淋巴瘤（MCL）、CAR-T初治队列及Waldenström巨球蛋白血症（WM）患者至少接受过1线治疗即可； * NHL患者既往接受过抗CD20单克隆抗体联合细胞毒性化疗； * MCL、CLL/SLL、WM及其他已批准BTK抑制剂适应证患者既往接受过BTK抑制剂；CLL/SLL患者接受过维奈克拉；费城染色体阳性（Ph+）B-ALL患者接受过酪氨酸激酶抑制剂； * 前线治疗未应答或治疗结束后12个月内复发；新诊断的CLL/SLL Richter转化或包括WM在内的惰性淋巴瘤转化除外； * 无快速进展疾病证据，以确保能够完成至少1个治疗周期； * 器官功能充分； * 白细胞计数≤20×10⁹/L； * 血小板≥30,000/μL。 排除标准： 疾病相关： * Burkitt淋巴瘤、原发性中枢神经系统（CNS）淋巴瘤、Richter转化为霍奇金淋巴瘤； * WM患者在NKX019首剂前<35天接受过血浆置换； * NHL患者存在活动性CNS恶性肿瘤证据； * B-ALL患者有髓外疾病（EMD）； * 既往接受过任何细胞治疗；但入组特定队列且要求既往CAR-T治疗、近期HCT或有HCT相关并发症者除外； * NKX019首剂前方案规定时间窗内接受过其他抗癌治疗； * 既往治疗导致的残留毒性≥2级； * 研究方案禁止的其他合并症或合并用药； * 妊娠或哺乳期女性。
Inclusion Criteria: General: Eastern Cooperative Oncology Group (ECOG) performance status ≤1 • Disease Related: * Have a histologically or cytologically confirmed diagnosis of r/r B cell NHL or CLL or B-ALL as defined by WHO 2016 classification * Subjects who received prior CD19/CD20-directed therapy must have disease that remains CD19+ and/or CD20+ respectively * Have measurable disease * Have received ≥2 lines of therapy except subjects with MCL, CAR T Naïve cohorts and WM, who must have received at least 1 prior line of therapy * Have received a combination of an anti CD20 monoclonal antibody and cytotoxic chemotherapy for subjects with NHL * Received: * BTKi for subjects with MCL, CLL/SLL, WM, and other indications where a BTKi is approved * Venetoclax for subjects with CLL/SLL * Tyrosine kinase inhibitor for subjects with Philadelphia chromosome (Ph+) B-ALL * Not responded or relapsed within 12 months of completion of their prior line of therapy, with the exception of a newly diagnosed Richter's transformation of CLL/SLL or other transformation of an indolent lymphoma, including from WM * Subjects must not have evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment. * Adequate organ function * White blood cell count of ≤20 × 109/L * Platelet count ≥30,000/uL Exclusion Criteria: • Disease related: * Burkitt Lymphoma, primary central nervous system (CNS) lymphoma, Richter's transformation to Hodgkin lymphoma * Subjects with WM who underwent plasmapheresis \<35 days prior to the first dose of NKX019 * Subjects with NHL with any evidence of active CNS malignancy * Subjects with B-ALL who have extramedullary disease (EMD) * Subjects with any prior cellular therapy except subjects enrolling in selected cohorts who must have received prior CAR T therapy, recent HCT, or complications from HCT * Recent use of any cancer-directed therapy within protocol specified window prior to the first dose of NKX019 * Residual toxicities ≥Grade 2 due to prior therapy * Other comorbid conditions and concomitant medications prohibited as per study protocol * Pregnant or lactating female
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：Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] · Incidence, nature, and severity of treatment related adverse events will be evaluated. An adverse event is any unfavorable and unintended sign including clinically significant abnormal laboratory findings, symptom or disease. · 30 days after last dose of NKX019；Proportion of subjects experiencing dose-limiting toxicities of NKX019 · DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria · 28 days from first dose of NKX019；Objective response rate to NKX019 in Part 2 · Percentage of subjects with complete and partial response. Response to treatment will be assessed based on: Lugano classification with LYRIC refinement for subjects with NHL (except CLL/SLL and WM); 2018 iwCLL guidelines for subjects with CLL/SLL; Version 1.2020 NCCN for subjects with B-ALL; consensus criteria from the 6th International Workshop on Waldenström Macroglobulinemia for subjects with WM. · Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]
次要终点：Assessment of NKX019 half-life；NKX019 duration of persistence；Evaluation of host immune response against NKX019；Objective response rate to NKX019 in Part 1
所有受试者接受氟达拉滨/环磷酰胺淋巴清除治疗，随后在28天周期的第0、7和14天每周接受一次NKX019，共3次。若开放联合治疗队列，则每个周期另联合利妥昔单抗。
这是一项单臂、开放标签、多中心I期研究，旨在确定试验性NKX019（靶向CD19的异基因CAR-NK细胞）治疗复发/难治性非霍奇金淋巴瘤（NHL）、慢性淋巴细胞白血病（CLL）或B细胞急性淋巴细胞白血病（B-ALL）患者的安全性和耐受性。
This is a single arm, open-label, multi-center, Phase 1 study to determine the safety and tolerability of an experimental therapy called NKX019 (allogeneic CAR NK cells targeting CD19) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B cell acute lymphoblastic leukemia (B-ALL)
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