肿瘤细胞治疗研究
英文原题：A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd)-Based Regimen Followed by BCMA CAR-T Therapy in Transplant-Ineligible Patients With Primary Plasma Cell Leukemia
⚠ 该试验的登记信息已有 14 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 BCMACAR-T 细胞治疗白血病的安全性、可行性及初步疗效。当前状态：招募中。计划入组 20 例。试验地点：中国 · 天津（共 1 个中心，其中中国 1 个）。登记号：NCT05979363。
不限性别 · ≥ 18 Years 且 ≤ 75 Years
纳入标准： 1. 年龄≥18岁且≤75岁。 2. 按IMWG诊断标准确诊原发性浆细胞白血病：外周血涂片形态学检测循环浆细胞≥5%，或外周血肿瘤性浆细胞绝对值>2×10⁹/L。 3. 筛选时有可测量疾病，符合至少一项：血清M蛋白≥1.0 g/dL或24小时尿M蛋白≥200 mg；或无可测量血清/尿病灶的轻链型骨髓瘤，血清免疫球蛋白游离轻链≥10 mg/dL且血清κ/λ游离轻链比值异常。 4. 不适合接受自体干细胞移植后的大剂量化疗，原因包括：年龄较大（≥65岁）；研究者评估不适合；ECOG体能状态3–4分；多次造血干细胞动员失败；或初始治疗阶段暂缓大剂量化疗/自体移植。 5. 流式细胞术或病理检查证实骨髓BCMA阳性。 6. 入组前14天内完成筛选生化检查：总胆红素<ULN的2倍（Gilbert综合征患者<3倍）；AST/ALT<ULN的3倍；按Cockcroft-Gault公式计算肌酐清除率≥30 mL/min。 7. 入组前7天内血常规符合，且此前14天内未输红细胞、使用G-CSF/GM-CSF/促血小板药物或药物纠正，前7天未输注血小板：WBC≥1.5×10⁹/L、ANC≥1.0×10⁹/L、血红蛋白≥70 g/L；若骨髓浆细胞<50%，血小板≥75×10⁹/L；若骨髓浆细胞≥50%，血小板≥50×10⁹/L。 8. 能按研究建议接受预防性抗凝治疗。 9. 女性不在哺乳期、未妊娠，并同意研究期间及之后12个月内不妊娠；男性同意配偶在研究期间及之后12个月内不妊娠。 排除标准： 1. 有明确活动性淀粉样变。 2. 有明确中枢神经系统受累。 3. 既往接受任何BCMA靶向治疗或CAR-T治疗。 4. 周围神经病变>2级，或基线时伴疼痛的>2级周围神经病变，不论是否正在接受治疗。 5. 已知对糖皮质激素、硼替佐米、来那度胺或BCMA CAR-T细胞产品不耐受、过敏或有禁忌。 6. HIV血清阳性；乙肝或丙肝感染。 7. 预期生存期<6个月。 8. 妊娠或哺乳期。 9. 活动性胃肠功能障碍，影响吞咽片剂或研究治疗药物吸收。 10. 随机分组前2周内接受重大手术（如全身麻醉），尚未完全康复，或计划研究期间手术。 11. 研究治疗前4周内接种活减毒疫苗。 12. 研究者认为会影响治疗、依从性或知情同意能力的严重精神/躯体疾病、症状或其他情况。 13. 必需药物或支持治疗与研究治疗存在禁忌。 14. 可能干扰研究的其他疾病或并发症。 15. 不愿或不能遵守研究方案。
Inclusion Criteria: 1. Age ≥ 18 years and ≤ 75 years. 2. Participants with documented primary plasma cell leukemia according to IMWG diagnostic criteria (circulating plasma cells ≥5%, determined by morphology on peripheral blood smear; or absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10\^9/L). 3. Measurable disease, at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio. 4. Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age (≥65); or Ineligible evaluated by researchers; or Eastern Cooperative Oncology Group Performance Status grade of 3 or 4; or Repeated hematopoietic stem cell mobilization failure； or Deferral of high-dose chemotherapy with ASCT as initial treatment. 5. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 6. All screening blood biochemistry: tests should be performed according to the protocol and within 14 days before enrollment. Screening laboratory values must meet the following criteria: a.TBIL\<2 x upper limit of normal (ULN) (\<3 x ULN in patients with Gilbert's syndrome); b.AST and ALT \<3 x ULN.; c. Creatinine clearance ≥ 30mL/min (calculated using Cockroft-Gault formula). 7. Routine blood tests (performed within 7 days, no RBC transfusion, no G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no PLT transfusion within 7 days) : WBC ≥ 1.5 x 109/L, ANC ≥ 1.0 x 109/L, Hb ≥ 70 g/L PLT ≥ 75 x 109/L (if BMPC \< 50%) or PLT ≥ 50 x 109/L (if BMPC ≥ 50%). 8. Patients must be able to take prophylactic anticoagulant therapy as recommended by the study. 9. The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during the study period and for the following 12 months. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter. Exclusion Criteria: 1. Documented active amyloidosis. 2. Documented with central nervous system (CNS) invasion. 3. Prior exposure to any BCMA-targeted therapy or CAR-T therapy. 4. Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy. 5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and BCMA-CART cellular products. 6. Seropositive for human immunodeficiency virus (HIV) 7. Hepatitis B infection 8. Hepatitis C infection 9. Life expectancy of \<6 months 10. Women who are pregnant or breastfeeding 11. Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that may affect the absorption of the studied treatment medication 12. Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or is not fully recovered from the surgery, or surgery is arranged during study period. 13. Received live attenuated vaccine within 4 weeks prior to study treatment. 14. According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent. 15. Necessary medication or supportive therapy is contraindicated with study treatment. 16. Any diseases or complications that may interfere with the study. 17. Patients are not willing to or cannot comply with study scheme.
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：Safety and Tolerability · The incidence of treatment-emergent adverse events (TEAEs) · Up to 2 year；MRD-negative rate · achieving MRD-negative, as determined by NGS/NGF after consolidation treatment · within 1 week after consolidation treatment
次要终点：Complete response rate (CRR)；Progression free survival (PFS)；Overall Survival (OS)；Duration of Remission(DOR)
VRd方案：硼替佐米1.3 mg/m²皮下注射（第1、8、15、22天），来那度胺25 mg口服（第1–21天），地塞米松40 mg（第1、8、15、22天），每周期28天。自体BCMA靶向CAR-T细胞以2–4×10⁶个抗BCMA CAR阳性T细胞/kg为目标剂量静脉输注。治疗顺序为VRd诱导、BCMA CAR-T输注、VR巩固及VR维持。
本单臂、开放标签研究评估基于VRd方案联合BCMA CAR-T治疗不适合移植的原发性浆细胞白血病患者的疗效和安全性。
This is a single-arm, open-label study to evaluate the efficacy and safety of VRD-based regimen combined with BCMA CAR-T in transplant-ineligible patients with primary plasma cell leukemia
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