肿瘤细胞治疗研究
英文原题：Sonrotoclax Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma Planned for Standard of Care CAR-T Cell Therapy
这是一项 II 期注册临床试验，评估细胞治疗用于套细胞淋巴瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 40 例。试验地点：其他 · 卡尔加里、埃德蒙顿、温哥华、多伦多（共 4 个中心）。登记号：NCT07341191。
不限性别 · ≥ 18 Years
纳入标准： * 经组织学确诊的套细胞淋巴瘤，且在至少一线既往全身治疗后复发或难治 * 适合并计划接受加拿大卫生部批准的 CAR-T 治疗。 * 有可用的福尔马林固定石蜡包埋肿瘤组织蜡块，且必须已提供同意释放该蜡块的知情同意书。 * 有影像学记录的疾病存在。 * 可测量病灶（至少一个部位可双径测量）。 * 年龄 ≥ 18 岁。 * ECOG 体能状态评分为 0、1 或 2 * 预期寿命 ≥ 6 个月 * 血液学和生化指标充足 * 必须已接受如下所示的既往全身治疗； * 至少一线全身治疗包括 Bruton 酪氨酸激酶抑制剂（BTKi）。 * 既往接受过 venetoclax、sonrotoclax 或任何其他 BCL2 抑制剂（BCL2i）的受试者符合入组条件，前提是未在末次 BCL2i 给药后 6 个月内发生疾病进展。在 BCL2i 治疗期间或末次给药后 6 个月内发生疾病进展的受试者不符合入组条件。 * 受试者必须在正在接受 BTKi 治疗期间进入研究，或入组本方案的子研究以接受 zanubrutinib 达到最短持续时间后，方可入组主研究。 * 既往曾暴露于 zanubrutinib 的受试者无论对治疗的应答如何均可入组。 * 在正在接受 BTKi 治疗期间进入研究的受试者，必须将其 BTKi 换为通过研究提供的 zanubrutinib。 * 受试者必须已从既往治疗相关的所有可逆性毒性中恢复至 ≤ 1 级。 * 必须按照方案进行充分的洗脱。 * 既往高剂量骨髓抑制性放疗允许在入组前 ≥28 天进行。 * 既往大手术允许在入组前 ≥28 天进行。有生育潜能的受试者必须同意使用高效避孕方法。 排除标准 * • 正在接受针对其他晚期或转移性恶性肿瘤的积极抗癌治疗的受试者。 * 同时接受其他抗癌治疗 * 严重疾病或医学状况，导致受试者无法按照方案进行管理。 * 已知对研究药物或其成分过敏。 * 既往任何时间接受过靶向 CD19 的 CAR-T 治疗、6 周内接受过自体造血细胞移植，或 3 个月内接受过异基因造血细胞移植。异基因造血细胞移植受者必须无临床显著的移植物抗宿主病（GvHD），且在入组前至少 4 周已停用 GvHD 免疫抑制治疗。 * 未经治疗和/或未控制的心血管疾病和/或有症状的心功能障碍（包括需要药物治疗的心室性心律失常、2 度或 3 度房室传导阻滞病史），或既往一年内有不稳定型心绞痛、充血性心力衰竭或心肌梗死。 * 入组前 14 天内存在活动性、未控制的细菌、真菌或病毒感染 * 妊娠期或哺乳期女性。 * 在 sonrotoclax 递增治疗期间无法停用中度或强效 CYP3A 诱导剂或抑制剂。 * 入组前 4 周内接种过活疫苗，或计划在治疗期间或末次给药后 90 天内接种活疫苗。 * 无法吞咽胶囊或片剂，或患有任何显著影响胃肠道功能的疾病 * 活动性中枢神经系统（CNS）疾病；CNS疾病稳定的受试者可入组。 * 入组前28天内使用过生长因子。
Inclusion Criteria: * Have histologically confirmed mantle cell lymphoma that is relapsed or refractory after at least one prior line of systemic therapy * Eligible for and planned to receive Health Canada approved CAR-T. * Have a formalin fixed paraffin embedded tumour tissue block available and must have provided informed consent for the release of the block. * Presence of radiologically documented disease. * Measurable disease (one site bidimensionally measurable). * Age ≥ 18 years. * Have an ECOG performance status of 0, 1 or 2 * Anticipated life expectancy of ≥ 6 months * Adequate hematologic and biochemical parameters * Must have received prior systemic therapy as shown below; * At least one line of systemic therapy including a Bruton's Tyrosine Kinase inhibitor (BTKi). * Participants who have previously received venetoclax, sonrotoclax, or any other BCL2 inhibitor (BCL2i) are eligible as long as progressive disease did not occur within 6 months of the last dose of BCL2i. Participants with progressive disease during BCL2i therapy or within 6 months of last dose are not eligible. * Participants must enter the study while on a BTKi or enroll to a substudy of the protocol to receive zanubrutinib for a minimum duration prior to enrolling to the main study. * Participants previously exposed to zanubrutinib are eligible irrespective of response to treatment. * Participants entering the study while on a BTKi must have their BTKi switched to zanubrutinib supplied through the study. * Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior therapies. * Adequate washout must be followed per protocol. * Prior high-dose myelosuppresive radiation is permitted ≥28 prior to enrollment. * Previous major surgery is permitted ≥28 days prior to enrollment. Participants of childbearing potential must have agreed to use a highly effective contraceptive method. Exclusion Criteria * • Participants on active anticancer therapy for other advanced or metastatic malignancies. * Concurrent treatment with other anti-cancer therapy * Serious illnesses or medical conditions which would not permit the participant to be managed according to the protocol. * Known hypersensitivity to the study drug(s) or their components. * Prior CD19-directed CAR-T at any time, autologous hematopoietic cell transplantation within 6 weeks, or allogeneic hematopoietic cell transplantation within 3 months. Allogeneic hematopoietic cell transplantation recipients must be free of clinically-significant graft-versus-host disease (GvHD) and must be off immunosuppression for GvHD for at least 4 weeks before enrollment. * Untreated and/or uncontrolled cardiovascular conditions and/or symptomatic cardiac dysfunction (including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or unstable angina congestive heart failure or myocardial infarction within the previous year. * Active, uncontrolled bacterial, fungal, or viral infection within 14 days prior to enrollment * Pregnant or breastfeeding women. * Inability to discontinue use of moderate or strong CYP3A inducers or inhibitors during the ramp-up treatment period with sonrotoclax. * Live vaccination within 4 weeks prior to enrollment or who plan to receive a live vaccine during treatment or within 90 days post last dose. * Inability to swallow capsules or tablets or have any diseases significantly affecting GI function * Active central nervous system (CNS) disease; Participants with stable CNS disease are eligible. * Growth factors within 28 days prior to enrollment.
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：Complete response post CAR-T · 3.5 years
次要终点：Objective Response Rate assessed by the Lugano Classification；1 year Progression-Free Survival；Overall Survival；Number and Severity of Adverse Events
本研究的目的是评估在套细胞淋巴瘤受试者的标准治疗嵌合抗原受体（CAR-T）细胞疗法基础上，联合两种口服药物（sonrotoclax 联合 zanubrutinib）的疗效。
The purpose of this study is to evaluate the effects of adding two oral medications (sonrotoclax plus zanubrutinib) to standard of care chimeric antigen receptor (CAR-T) cell therapy in participants with mantle cell lymphoma.
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