肿瘤细胞治疗研究
英文原题：A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Relapsed Refractory Multiple Myeloma (DURGA-4)
这是一项 III 期注册临床试验，评估细胞治疗用于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 508 例。试验地点：中国 · 北京、长春、长沙、重庆（共 143 个中心，其中中国 27 个）。登记号：NCT07391657。
不限性别 · ≥ 18 Years
纳入标准： * 年龄 ≥ 18 岁 * 根据 IMWG 诊断标准，有记录的多发性骨髓瘤诊断 * 有记录的可测量疾病证据： 1. 血清 M 蛋白水平 ≥ 1 g/dL 2. 尿 M 蛋白水平 ≥ 200 mg/24h 3. 血清免疫球蛋白游离轻链 ≥ 10 mg/dL（100 mg/L）且血清免疫球蛋白 kappa lambda 游离轻链比值异常 * 根据研究者判断，在最近一线治疗期间或之后，有记录的符合 IMWG 2016 标准的 PD 证据。仅接受过 1 线既往治疗的参与者必须在干细胞移植后 47 个月内出现进展，或如果未接受移植，则在开始初始治疗后 42 个月内出现进展 * 接受过 1 至 3 线既往治疗，包括 IMiD 以及 PI 或 CD38 抗体。参与者必须对每线治疗至少完成 2 个完整周期的治疗，除非 PD 是该线治疗的最佳缓解 * 根据研究者判断，有资格接受至少一种标准方案（DKd、PVd、DPd 或 Kd）。 * ECOG 体能状态评分为 0 至 1 * 血液学和生化实验室检查值充分： 1. 血红蛋白 ≥ 8.0 g/dL 2. 中性粒细胞绝对计数 ≥ 1 × 10^9/L（1000/mm3） 3. 在骨髓有核细胞中浆细胞 < 50% 的参与者中，血小板计数 ≥ 75 × 10^9/L（75000/mm3），或在骨髓有核细胞中浆细胞 ≥ 50% 的参与者中，血小板计数 ≥ 50 × 10^9/L（50000/mm3） 4. 淋巴细胞绝对计数 ≥ 300/µL（0.3 × 109/L） 5. 无 Gilbert 综合征时总胆红素 ≤ 1.5 × ULN，或如果参与者有 Gilbert 综合征，则 ≤ 3 × ULN。AST 和 ALT ≤ 3.0 × ULN。采用 Cockcroft 和 Gault 方法计算的 CrCl ≥ 30 mL/分钟 排除标准： * 已知活动性或既往有 CNS 受累史，或表现出 MM 脑膜受累的临床体征。 * 原发性淀粉样变性、活动性浆细胞白血病、Waldenstrom 巨球蛋白血症或多发性神经病、器官肿大、内分泌病、M 蛋白和皮肤改变（POEMS）综合征。 * 原发性难治性 MM 的参与者（对任何既往治疗未能产生至少最小缓解） * 显著神经或精神疾病 * 使参与者处于治疗相关并发症不可接受风险中的显著医学状况 * 既往接受过任何 BCMA 靶向治疗 * 既往接受过针对任何靶点的 CAR-T 或 CAR-NK 治疗 * 既往接受过针对任何靶点的 T 细胞衔接器治疗 * 在既往治疗期间任何时间接受过异基因干细胞移植，或在随机化前 12 周内接受过自体干细胞移植
Inclusion Criteria: * Age ≥ 18 years * Documented diagnosis of multiple myeloma according to the IMWG diagnostic criteria * Documented evidence of measurable disease: 1. Serum M-protein level ≥ 1 g/dL 2. Urine M-protein level ≥ 200 mg/24h 3. Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio * Documented evidence of PD by IMWG 2016 criteria based on investigator's determination during or after the most recent line of therapy. Participants with only 1 prior line of therapy must have progressed within 47 months of a stem cell transplant, or if not transplanted, then within 42 months of starting initial therapy * Received 1 to 3 lines of prior therapy including an IMiD and either a PI or a CD38 antibody. Participant must have undergone at least 2 complete cycles of treatment for each line of therapy, unless PD was the best response to the line of therapy * Eligible to receive at least one of the standard regimens (DKd, PVd, DPd, or Kd) as determined by the Investigator. * ECOG performance status score of 0 to 1 * Adequate hematology and chemistry laboratory values: 1. Haemoglobin ≥ 8.0 g/dL 2. Absolute neutrophil count ≥ 1 × 10\^9/L (1000 per mm3) 3. Platelet count ≥ 75 × 10\^9/L (75000 per mm3) in participants with \< 50% of bone marrow nucleated cells are plasma cells or ≥ 50 × 10\^9/L (50000 per mm3) in participants with ≥ 50% of bone marrow nucleated cells are plasma cells 4. Absolute lymphocyte count ≥ 300/µL (0.3 × 109/L) 5. Total bilirubin ≤ 1.5 × ULN in the absence of Gilbert's syndrome or ≤ 3 × ULN if the participant has Gilbert's syndrome. AST and ALT≤ 3.0 × ULN. CrCl by Cockcroft and Gault method ≥ 30 mL/minute Exclusion Criteria: * Known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM. * Primary amyloidosis, active plasma cell leukaemia, Waldenstrom macroglobulinemia or Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin (POEMS) syndrome. * Participants with primary refractory MM (failed to generate at least a minimal response to any prior therapy) * Significant neurological or psychiatric condition * Significant medical condition that places the participant at an unacceptable risk for treatment-related complications * Previously received any prior BCMA-targeted treatment * Previously received CAR-T or CAR-NK therapy directed at any target * Previously received T-cell engager therapy directed at any target * Previously received allogeneic stem cell transplantation at any time during prior therapy or received autologous stem cell transplantation within 12 weeks of randomization
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：To demonstrate the superiority of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of PFS in participants with RRMM. · PFS: defined as time from randomisation until progression according to IMWG 2016 criteria as assessed by BICR, or death due to any cause, whichever occurs first. · 3 years；To demonstrate the superiority of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of MRD negativity rate at 9 months in participants with RRMM. · MRD negative CR rate at 9 months: defined as the proportion of participants with MRD negative status and have a response of CR or sCR (according to the IMWG 2016 criteria) at 9 months (± 3 months) from randomisation before initiation of subsequent anti-myeloma therapy. · 2 years
次要终点：To further demonstrate the effectiveness of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of CRR in participants with RRMM.；To further demonstrate the effectiveness of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of ORR in participants with RRMM.；To further demonstrate the effectiveness of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of OS in participants with RRMM.
AZD0120
由研究者选择以下4种标准方案之一；DKd、DPd、PVd、Kd。
这是一项随机、多中心、对照、开放标签的III期全球研究，旨在比较AZD0120与标准方案（DKd[达雷妥尤单抗、卡非佐米和地塞米松]、DPd[达雷妥尤单抗、泊马度胺和地塞米松]、PVd[泊马度胺、硼替佐米和地塞米松]或Kd[卡非佐米和地塞米松]）在RRMM参与者中的疗效和安全性。
This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of AZD0120 versus standard regimens (DKd \[daratumumab, carfilzomib, and dexamethasone\], DPd \[daratumumab, pomalidomide, and dexamethasone\], PVd \[pomalidomide, bortezomib and dexamethasone\], or Kd \[carfilzomib and dexamethasone\]) in participants with RRMM.
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