肿瘤细胞治疗研究
英文原题：Anti BCMA CAR- T Cell Therapy for Adults With Relapsed or Refractory Multiple Myeloma
这是一项 I/II 期注册临床试验，评估 BCMACAR-T 细胞治疗多发性骨髓瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 30 例。试验地点：其他 · 明斯克（共 1 个中心）。登记号：NCT07477912。
不限性别 · ≥ 18 Years
纳入标准： 1. 年龄≥18岁，男女均可； 2. 愿意且能够提供书面知情同意； 3. ECOG体能状态评分0–2分； 4. 按IMWG标准确诊复发/难治性多发性骨髓瘤，既往接受过2线治疗，且对蛋白酶体抑制剂和免疫调节剂耐药； 5. 器官系统功能充分，包括：肌酐清除率≥30 cc/min；血清ALT/AST≤2.5×ULN；总胆红素≤1.5×ULN，Gilbert综合征患者除外；超声心动图（ECHO）测得左心室射血分数（LVEF）≥50%；室内空气下基线血氧饱和度>92%，呼吸困难≤1级； 6. 无活动性GVHD（2–4级）； 7. 骨髓功能充分：中性粒细胞绝对计数≥1.0×10⁹/L；淋巴细胞绝对计数≥0.3×10⁹/L（入组及白细胞单采前均须满足）；血红蛋白≥80 g/L；血小板≥50×10⁹/L。 排除标准： 1. 妊娠或哺乳期女性； 2. 有临床相关CNS病变史或目前存在此类病变，如癫痫、轻瘫、失语、过去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、未控制精神疾病或精神病； 3. 恶性肿瘤活动性CNS受累。既往有CNS受累者，如疾病已得到有效治疗，且治疗距入组至少4周（距CAR-T输注至少8周），可符合入组条件； 4. 有临床意义且未控制的心脏病，或近期（12个月内）发生心脏事件； 5. 需要全身治疗的活动性细菌、病毒或真菌感染；活动性或潜伏性乙肝、丙肝；HIV、人T细胞淋巴瘤病毒（HTLV-1/2）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/疾病修饰药物治疗的自身免疫性疾病史； 7. 筛查胸部CT提示活动性肺炎，或有药物性肺炎、特发性肺纤维化、机化性肺炎或特发性肺炎史； 8. 其他恶性肿瘤史，除非无病至少24个月。原位癌、非黑色素瘤皮肤癌以及接受激素治疗的乳腺癌或前列腺癌允许； 9. 以下禁用药物：白细胞单采前7天或CAR-T给药前72小时内使用治疗剂量类固醇（生理替代、局部及吸入性类固醇允许）；免疫抑制药物须在白细胞单采或CAR-T输注前≥2周停用；CAR-T输注前1周及白细胞单采前1周内使用细胞毒性化疗；白细胞单采前14天内使用粒细胞集落刺激因子；入组前≤4周内接种活疫苗；开始预处理化疗前4周内鞘内预防性治疗使用甲氨蝶呤，或前2周内使用其他鞘内化疗（如阿糖胞苷）；CAR-T细胞输注前2周内接受过有限范围放疗； 10. 既往接受过抗BCMA治疗； 11. 已知对人血清白蛋白、二甲基亚砜（DMSO）、环磷酰胺、氟达拉滨或托珠单抗过敏； 12. 研究者认为不适合参加临床试验的其他情况。
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 2. 4. Relapsed or refractory multiple myeloma according to IMWG criteria with two previous lines of therapy and resistance to proteosome inhibitors and immunomodulators. 5. Adequate organ system function including \- Creatinine clearance ≥30 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 ≥50 × 10\^9/L 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. * 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. Prior anti BCMA therapy 10. Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine or tocilizumab. 11\. 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, ICAHT and ASCTC. · 1 month post CAR-T cells infusion；Phase II. Overall response rate · partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR) rates according to IMVG criteria · 12 months post CAR-T cells infusion
次要终点：Phase I. duration of expansion of CAR-T cells；Phase II. Efficacy: Overall survival rates；Phase II. Progression-free survival rates；Phase II. Duration of response；Phase I. Peak of expansion of CAR-T cells
本研究主要旨在评估抗BCMA CAR-T细胞免疫治疗成人复发或难治性多发性骨髓瘤的安全性和疗效。
The mail purpose of this study is to estimate the safety and the efficacy of anti-BCMA CAR- T cell immunotherapy for adults with relapsed or refractory multiple myeloma
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