肿瘤细胞治疗研究
英文原题：Bispecific Antibody-Based Salvage Therapy Followed by CAR-T ± ASCT in R/R Aggressive B-Cell Lymphoma
Bispecific Antibody-Based Salvage Therapy Followed by CAR-T ± ASCT in R/R Aggressive B-Cell Lymphoma
⚠ 该试验的登记信息已有 16 个月未更新， 页面上显示的「招募中」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 II 期注册临床试验，评估 CAR-T 细胞治疗 B 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 25 例。试验地点：中国 · 天津（共 1 个中心，其中中国 1 个）。登记号：NCT06996132。
不限性别 · ≥ 18 Years 且 ≤ 65 Years
纳入标准： 1. 复发/难治性侵袭性B细胞淋巴瘤，包括弥漫大B细胞淋巴瘤（DLBCL）、高级别B细胞淋巴瘤（HGBL）或转化性大B细胞淋巴瘤。 2. 符合下列队列之一的复发/难治性疾病： 队列1（复发/难治性疾病）：既往接受≥2线治疗（包括抗CD20单克隆抗体和蒽环类化疗）且末次治疗后有记录的疾病进展；或一线免疫化疗（含抗CD20抗体和蒽环类药物）失败，定义为治疗结束后12个月内复发/进展、一线治疗期间进展、4个周期后最佳疗效为疾病稳定，或6个周期后最佳疗效为部分缓解。 队列2（早期治疗失败）：接受2个周期一线免疫化疗后PET-CT仍有Deauville评分5的代谢活性，或初始治疗后活检证实有残留病灶。 3. 年龄18–65岁（含）。 4. ECOG体能状态≤2。 5. 筛选时血液学指标达标（骨髓受累所致者除外）：中性粒细胞绝对计数（ANC）≥1×10⁹/L，血小板≥75×10⁹/L。 6. 筛选时生化指标达标：ALT、AST≤正常值上限（ULN）的3倍；总胆红素≤ULN的1.5倍（Gilbert综合征或非肝脏原因所致者除外）；血清肌酐≤ULN的2倍，或肌酐清除率≥40 mL/min。 7. 超声心动图测得的左心室射血分数（LVEF）处于本机构正常范围。 8. 室内空气下基线血氧饱和度>92%。 9. 研究者评估预期生存期≥3个月。 排除标准： 1. 已确诊原发性中枢神经系统淋巴瘤。 2. 既往接受自体或异基因造血干细胞移植。 3. 活动性乙肝或丙肝感染，定义为HBV-DNA或HCV-RNA水平高于检测上限。 4. 未控制的合并症，包括感染性疾病、心脑血管疾病、凝血障碍或结缔组织病。 5. 有癫痫或其他中枢神经系统疾病史。 6. 妊娠或哺乳期。 7. HIV感染。 8. 有其他恶性肿瘤史，但符合以下情况之一者除外：无病生存≥5年；或既往已治愈的非黑色素瘤皮肤癌（基底细胞癌、鳞状细胞癌或相关局限性皮肤恶性肿瘤）或宫颈原位癌。 9. 研究者判定不适合入组的其他情况。
Inclusion Criteria:
1. Patients with relapsed/refractory aggressive B-cell lymphoma, including the following subtypes: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), or transformed large B-cell lymphoma.
2. Relapsed or refractory disease, meeting criteria for one of the following cohorts:
Cohort 1 (Relapsed/Refractory Disease):
1. ≥2 prior lines of therapy (including both anti-CD20 monoclonal antibody and anthracycline-based chemotherapy) with documented progression following last treatment; OR
2. Failure of first-line immunochemotherapy (containing anti-CD20 antibody and anthracycline) defined by any of:
* Relapse/progression within 12 months of treatment completion; OR
* Progressive disease during first-line therapy; OR
* Stable disease as best response after 4 cycles; OR
* Partial response as best response after 6 cycles.
Cohort 2 (Early Treatment Failure):
* Persistent metabolic activity (Deauville 5) on PET-CT after 2 cycles of first-line immunochemotherapy; OR
* Biopsy-proven residual disease following initial therapy.
3. Age ≥18 years and ≤65 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
5. Hematologic parameters at screening must meet the following (unless due to bone marrow involvement):
* Absolute neutrophil count (ANC) ≥1×10⁹/L,
* Platelet count (PLT) ≥75×10⁹/L.
6. Biochemical parameters at screening must meet the following:
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN);
* Total bilirubin (TBIL) ≤1.5×ULN (unless due to Gilbert's syndrome or non-hepatic causes);
* Serum creatinine (Cr) ≤2×ULN OR creatinine clearance ≥40 mL/min.
7. Left ventricular ejection fraction (LVEF) within institutional normal range by echocardiography.
8. Baseline oxygen saturation \>92% on room air.
9. Life expectancy ≥3 months as assessed by the investigator.
Exclusion Criteria:
1. Confirmed primary central nervous system lymphoma;
2. Prior autologous or allogeneic hematopoietic stem cell transplantation;
3. Active HBV or HCV infection, defined as HBV-DNA or HCV-RNA levels above the upper limit of detection.
4. Uncontrolled comorbidities include infectious diseases, cardiovascular/cerebrovascular disorders, coagulopathies, and connective tissue diseases.
5. History of epilepsy or other central nervous system disorders;
6. Pregnancy or lactation;
7. HIV infection;
8. History of other malignancies unless:
1. Disease-free for ≥5 years, or
2. Previously cured of the following:
* Non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma, or related localized cutaneous malignancies)
* Carcinoma in situ of cervix
9. Other conditions deemed ineligible by investigators.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 rate after CAR-T±ASCT · The complete response (CR) rate after CAR-T±ASCT is defined as the proportion of subjects achieving CR following CAR-T with or without ASCT. · From CAR-T±ASCT administration until 1 year post-treatment
次要终点：overall response rate after CAR-T±ASCT；complete response rate before CAR-T±ASCT；overall response rate before CAR-T±ASCT；progression free survival-total (PFS-t）；progression free survival-CART (PFS-c）
受试者先接受2个周期格菲妥单抗为基础的治疗，随后接受CAR-T细胞治疗，或接受CAR-T联合ASCT。
本研究包含两个连续治疗阶段。第一阶段，复发/难治性侵袭性B细胞非霍奇金淋巴瘤患者接受2个周期格菲妥单抗，可联合研究者选定的药物。第二阶段，适合接受CAR-T单药的患者先接受氟达拉滨/环磷酰胺（FC）淋巴细胞清除治疗，再输注CAR-T（2–4×10⁶/kg）；适合接受CAR-T联合自体造血干细胞移植（ASCT）的患者接受预处理化疗，第0天回输外周血干细胞，第+3天（±1天）给予CAR-T（2–4×10⁶/kg）。CAR-T输注后第28天Deauville评分为4–5或循环肿瘤DNA（ctDNA）阳性的患者，随后接受4个周期格菲妥单抗巩固治疗。
This study consists of two sequential treatment phases. In the first phase, patients with r/r aggressive B-NHL receive two cycles of glofitamab ± investigator-selected agents. In the second phase, patients eligible for CAR-T monotherapy undergo FC lymphodepletion followed by CAR-T infusion (2-4×10⁶/kg), while those eligible for CAR-T+ASCT receive conditioning chemotherapy with PBSC reinfusion on day 0 and CAR-T administration (2-4×10⁶/kg) on day +3 (±1). Patients demonstrating Deauville 4-5 or ctDNA positivity at day 28 post-CAR-T infusion subsequently receive four cycles of glofitamab consolidation therapy.
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