肿瘤细胞治疗研究
英文原题：This is a Phase I/II Interventional, Open-label Treatment Study Designed to Evaluate the Safety and Efficacy of Anti CD 19/22 CAR- T Cells Immunotherapy for Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia/Lymphoma.
⚠ 该试验的登记信息已有 13 个月未更新， 页面上显示的「尚未开始招募」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 CD19CAR-T 细胞治疗白血病、B 细胞淋巴瘤的安全性、可行性及初步疗效。当前状态：尚未开始招募。计划入组 17 例。试验地点：其他 · 明斯克（共 1 个中心）。登记号：NCT07162571。
不限性别 · ≥ 18 Years
纳入标准： 1. 男性或女性，年龄≥18岁。 2. 愿意且能够提供书面知情同意。 3. 东部肿瘤协作组（ECOG）体能状态评分为0至1。 4. 复发性或难治性淋巴细胞白血病/淋巴瘤。 - 接受≥1线治疗后化疗难治性疾病 - 化疗后或ASCT/Allo-HSCT后复发。 5. 器官系统功能充分，包括 - 肌酐清除率≥40 cc/min。 - 血清丙氨酸氨基转移酶/天冬氨酸氨基转移酶≤2.5×正常值上限（ULN）。 - 总胆红素≤1.5×ULN，Gilbert综合征受试者除外。 - 左心室射血分数（LVEF）≥50%（通过超声心动图[ECHO]或 - 基线室内空气下血氧饱和度>92%且呼吸困难≤1级。 6. 无活动性GVHD（2-4级） 7. 骨髓（BM）功能充分 - 中性粒细胞绝对计数≥1.0×10^9/L。 * 淋巴细胞绝对计数≥0.3×10^9/L（入组时及白细胞分离术前）。 * 血红蛋白≥80 g/L。 * 血小板≥75×10^9/L 7. 通过免疫组织化学或流式细胞术报告肿瘤细胞上CD19和/或CD22表达为阳性 排除标准： 1. 妊娠或哺乳期女性。 2. 具有临床相关的中枢神经系统病理学病史或存在，如癫痫、瘫痪、失语、既往3个月内卒中、严重脑损伤、痴呆、帕金森病、小脑疾病、器质性脑综合征、未控制的精神疾病或精神病。 3. 恶性肿瘤活动性中枢神经系统受累的患者。有恶性肿瘤中枢神经系统（CNS）受累史的患者，如果CNS疾病已得到有效治疗，且治疗至少在入组前4周（至少在CAR-T输注前8周），则可能符合资格。 4. 具有临床意义的、未控制的心脏病或近期（12个月内）心脏事件。 5. 需要全身治疗的活动性细菌、病毒或真菌感染。活动性或潜伏性乙型肝炎感染或丙型肝炎感染。人类免疫缺陷病毒、人类T细胞淋巴病毒（HTLV1和2）或梅毒检测阳性。 6. 过去24个月内有导致终末器官损伤或需要全身免疫抑制/全身疾病调节剂的自身免疫性疾病史。 6. 筛选时胸部计算机断层扫描（CT）显示活动性肺炎证据，或药物性肺炎、特发性肺纤维化、机化性肺炎或特发性肺炎病史。 7. 其他恶性肿瘤病史，除非无病生存至少24个月（允许原位癌、非黑色素瘤皮肤癌、接受激素治疗的乳腺癌或前列腺癌）。 8. 以下药物排除： * 类固醇：白细胞分离术前7天内或CAR-T给药前72小时内使用治疗剂量的皮质类固醇。但是，允许生理替代、局部和吸入性类固醇。 * 免疫抑制：免疫抑制药物必须在白细胞分离术或CAR-T细胞输注前至少2周停止。 * 在CAR-T细胞输注前1周内和白细胞分离术前1周内接受过细胞毒性化疗。 * 在CAR-T细胞输注前2周内使用过抗体治疗，包括抗CD20/19/22治疗。 * 在白细胞分离术前不到14天使用过粒细胞集落刺激因子。 * 入组前≤4周接种过活疫苗。 * 预防性鞘内治疗：在开始预处理化疗前4周内使用过甲氨蝶呤，2周内使用过其他鞘内化疗（如Ara-C）。 在CAR-T细胞输注前2周内接受过局限性放疗。9. 已知对白蛋白、二甲基亚砜（DMSO）、环磷酰胺或氟达拉滨或托珠单抗过敏。 10. 研究者认为任何其他会使患者不适合参加本临床试验的情况。
Inclusion Criteria: 1. Male or female, aged ≥18 years. 2. Willing and able to give written, informed consent. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1. 4. Relapsed or refractory lymphoblastic leukemia/lymphoma. \- Chemotherapy-refractory disease after ≥1 lines of therapy \- Relapse after chemotherapy or after ASCT/Allo-HSCT. 5. Adequate organ system function including - Creatinine clearance ≥40 cc/min. \- Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x upper limit of normal (ULN). \- Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome. \- Left ventricular ejection fraction (LVEF) ≥50% (by echocardiogram \[ECHO\] or \- Baseline oxygen saturation \>92% on room air and ≤Grade 1 dyspnoea. 6. Have no active GVHD (Grade 2-4) 7. Adequate bone marrow (BM) function - Absolute neutrophil count ≥1.0 × 10\^9/L. * Absolute lymphocyte count ≥0.3 × 10\^9/L (at enrolment and prior to leukapheresis). * Haemoglobin ≥80 g/L. * Platelets ≥75 × 10\^9/L 7\. The expression of CD19 and/or CD22 on the tumor cells are reported as positive by either immunohistochemistry or flow cytometry Exclusion Criteria: 1. Females who are pregnant or lactating. 2. History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis. 3. Patients with active CNS involvement by malignancy. Patients with history of central nervous system (CNS) involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to CAR-T infusion). 4. Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event. 5. Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis. 6. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months. 6\. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis. 7\. History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed). 8\. The following medications are excluded: * Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to CAR-T administration. However, physiological replacement, topical, and inhaled steroids are permitted. * Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or CAR-T cells infusion. * Cytotoxic chemotherapies within 1 week of CAR-T cellsinfusion and 1 week prior to leukapheresis. * Antibody therapy use including anti-CD20/19/22 therapy within 2 weeks prior to CAR-T cells infusion. * Granulocyte-colony stimulating factor less than 14 days prior to leukapheresis. * Live vaccine ≤4 weeks prior to enrolment. * Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy. Prior limited radiation therapy within 2 weeks of CAR-T cells infusion. 9. Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine or tocilizumab. 10\. Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial.
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：Phase I. Safety · Number of Participants With Grade 3-5 Toxicities. Adverse events will be graded according to the CTCAE v5.0 · 1 month post CAR-T cells infusion；Phase II. Overall response rate · Including complete response (CR) and partial response (PR) rates · 3 months post CAR-T cells infusion
次要终点：Phase I. CAR-T proliferation；Phase II. Efficacy: Overall survival rates；Phase II. Progression-free survival rates；Phase II. Duration of response
本研究的目的是评估抗CD19/22 CAR-T细胞免疫疗法对复发或难治性急性淋巴细胞白血病/淋巴瘤成年患者的安全性和有效性。
The purpose of this study is to estimate the safety and the efficacy of anti-CD19/22 CAR- T cells immunotherapy for adults with relapsed or refractory acute lymphoblastic leukemia/lymphoma.
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