Rationale and design of DUAL study: Doxycycline to Upgrade response in light chain (AL) amyloidosis (DUAL): A phase 2 pilot study of a two-pronged approach of prolonged doxycycline with plasma cell-directed therapy in the treatment of AL amyloidosis.
Rationale and design of DUAL study: Doxycycline to Upgrade response in light chain (AL) amyloidosis (DUAL): A phase 2 pilot study of a two-pronged approach of prolonged doxycycline with plasma cell-directed therapy in the treatment of AL amyloidosis.
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DOI：
10.1016/j.conctc.2017.08.012
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发表时间：
2017-12
影响因子：
1.5
通讯作者：
Hari P
中科院分区：
文献类型：
--
作者：
D'Souza A;Flynn K;Chhabra S;Dhakal B;Hamadani M;Jacobsen K;Pasquini M;Weihrauch D;Hari P
轻链淀粉样变性是一种浆细胞肿瘤，与系统性克隆性免疫球蛋白链的不溶性纤维沉积有关。由于晚期器官沉积以及缺乏经证实的去纤维化疗法，该疾病与高早期死亡率和发病率相关。临床前和回顾性临床数据表明，多西环素对AL淀粉样变性有益。正在进行的DUAL研究是一项单中心、开放标签、II期研究，其中正在接受基础肿瘤克隆定向治疗的AL淀粉样变性患者口服多西环素1年，以检验长期使用多西环素安全、可行并导致系统性AL淀粉样变性早期死亡率降低和加速器官淀粉样反应的假设。对于全身性AL患者，将每月进行一次临床随访访视，对于局限性AL患者，将每3个月进行一次临床随访访视。将在这些时间点采集血液检查结果，用于血液学缓解评估。每3个月进行一次器官检查，每6个月进行一次放射学检查。将在基线、6个月和12个月时采集研究血样。其他相关研究包括基质金属蛋白酶（MMP），金属蛋白酶组织抑制剂（TIMP）检测和患者报告的结果。
Light chain (AL) amyloidosis is a plasma cell neoplasm associated with insoluble fibril deposition from clonal immunoglobulin chains systemically. The disease is associated with high early mortality and morbidity owing to advanced organ deposition as well as lack of proven de-fibrillogenic therapies. Pre-clinical and retrospective clinical data suggests that doxycycline has benefit in AL amyloidosis. The ongoing DUAL study is a single center, open label, phase 2 study in which patients with AL amyloidosis who are undergoing clone-directed therapy for the underlying neoplasm with oral doxycycline given for 1 year to test the hypothesis that prolonged doxycycline use will be safe, feasible, and lead to reduced early mortality in systemic AL amyloidosis and hasten organ amyloid response. Clinical follow up visits will occur at monthly intervals for systemic AL patients and at 3 monthly intervals for localized AL patients. Blood tests will be collected during these time points for hematologic response assessment. Organ testing will be conducted at 3 monthly intervals and radiologic testing will be conducted at 6 monthly intervals. Research blood samples will be collected at baseline, 6 and 12 months. Other correlative studies include matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP) testing and patient-reported outcomes.