决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Preconditioning With a Combination of Thiotepa, Cyclophosphamide, and Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of NK/T-Cell Lymphoma
这是一项 II 期注册临床试验,评估细胞治疗用于淋巴瘤的安全性、可行性及初步疗效。当前状态:尚未开始招募。计划入组 37 例。登记号:NCT07276737。
不限性别 · ≥ 18 Years 且 ≤ 70 Years
纳入标准:年龄18-70岁,性别不限;经组织病理或流式细胞术诊断NK/T细胞淋巴瘤:III/IV期患者经一线或挽救治疗达到缓解;II期患者挽救治疗后复发/难治但达到缓解;NK细胞淋巴瘤/白血病患者一线或挽救治疗后达到缓解;或复发/难治性疾病。须有合适造血干细胞供者:亲属供者在HLA-A、-B、-C、-DQB1和-DRB1位点至少5/10匹配;无关供者至少8/10匹配。HCT特异性合并症指数(HCT-CI)≤2;ECOG 0-2分;肝肾、心肺功能符合:血清肌酐≤正常值上限1.5倍;射血分数≥50%;基础血氧饱和度>92%;总胆红素≤正常值上限1.5倍,ALT和AST≤2倍;肺功能DLCO(血红蛋白校正)≥40%且FEV1≥50%;能够理解并愿意参加研究,签署知情同意书。排除标准:对噻替哌、环磷酰胺或白消安及其成分过敏;任何不稳定系统性疾病,包括不稳定型心绞痛、筛查前3个月内脑血管意外或短暂性脑缺血、筛查前3个月内心肌梗死、NYHA≥III级充血性心力衰竭、需药物治疗的严重心律失常、肝肾或代谢性疾病、肺动脉高压;活动性未控制感染(与感染相关的血流动力学不稳定、感染症状/体征恶化、新发影像学感染灶,或原因未明且未排除感染的持续发热);≥2级癫痫、瘫痪、失语、新发脑梗死、严重脑外伤、痴呆、帕金森病或精神分裂症;HIV感染;需抗病毒治疗的活动性HBV或HCV感染,或HBsAg/乙肝核心抗体阳性且未接受抗乙肝病毒治疗、存在HBV再激活风险;妊娠或哺乳;有生育能力者不愿在治疗期间及治疗后12个月内避孕;研究者判定不宜入组的其他情况。
Inclusion Criteria: 1\. Age range: 18-70 years old, gender not restricted. 2. Patients diagnosed with NK/T cell lymphoma through histopathology or flow cytometry, 1) with stage III/IV patients receiving first-line or salvage treatment and achieving remission, 2) stage II patients with relapsed/refractory disease after salvage treatment achieving remission, 3) patients with NK cell lymphoma/leukemia receiving first-line or salvage treatment and achieving remission, 4) patients with relapsed/refractory disease. 3. Patients must have a suitable hematopoietic stem cell donor. 1) The related donor must have at least 5/10 HLA-A, -B, -C, -DQB1, and -DRB1 matching. 2) The unrelated donor must have at least 8/10 HLA-A, -B, -C, -DQB1, and -DRB1 matching. 4. HCT-specific comorbidity index score (HCT-CI) \<= 2. 5. ECOG: 0-2 points. 6. Liver and kidney functions, as well as heart and lung functions, must meet the following requirements: 1) Serum creatinine \<= 1.5 × ULN; 2) Cardiac function: Ejection fraction \>= 50%; 3) Basal oxygen saturation \> 92%; 4) Total bilirubin \<= 1.5 × ULN; ALT and AST \<= 2.0 × ULN; 5) Pulmonary function: DLCO (hemoglobin corrected) \>= 40% and FEV1 \>= 50%. 7. Patients must be capable of understanding and willing to participate in this study, and sign the informed consent form. Exclusion Criteria: 1\. Patients allergic to stietap, cyclophosphamide or busulfan or its components. 2. Any unstable systemic diseases: including but not limited to unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 3 months before screening), myocardial infarction (within 3 months before screening), congestive heart failure (NYHA classification ≥ III), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases;patients with pulmonary hypertension. 3. Active and uncontrolled infections: hemodynamic instability related to infection, or new symptoms or signs of infection worsening, or new infection lesions found on imaging, persistent fever without exclusion of infection without symptoms or signs; 4. Grade 2 or higher epilepsy, paralysis, aphasia, new cerebral infarction, severe brain trauma, dementia, Parkinson's disease, schizophrenia 5. HIV-infected patients; 6. Patients with active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral treatment; 2.patients with a risk of HBV activation, referring to those with positive hepatitis B surface antigen or core antibody but not receiving anti-hepatitis virus treatment; 7. Pregnant or lactating women; 8. Male and female individuals with reproductive capacity who are unwilling to use contraceptive methods during treatment and within 12 months after treatment; 9. Patients whose study investigators assess have other inadvisable inclusion conditions. \-
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:progression free survival · Two years after the transplantation
次要终点:Cumulative recurrence rate;Incidence of acute GVHD
评估噻替哌联合环磷酰胺和白消安作为异体造血干细胞移植(allo-HSCT)前预处理方案治疗NK/T细胞淋巴瘤的疗效和安全性。
Evaluation of the efficacy and safety of Thiotepa combined with Cyclophosphamide and Busulfan as conditioning regimen before allo-HSCT for the treatment of NK/T cell lymphoma
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