Comparison of Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy With or Without Doxycycline in Newly Diagnosed Mayo Stage II-III Light Chain Amyloidosis Patients: A Multi-center Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Progression-free survival
研究概览
简要总结
Survival of intermediate and high-risk primary light chain amyloidosis (pAL) remains poor due to high mortality within 3-6 months of diagnosis. Rapidly effective regimens such as bortezomib, cyclophosphamide and dexamethasone (BCD) still failed to overcome the poor prognosis in very advanced pAL amyloidosis patients. Recently, doxycycline was demonstrated to induce disruption of fibril formation and reduce the number of intact fibrils in transgenic mouse model of pAL amyloidosis. Furthermore, case-control study suggested that adjuvant oral doxycycline could improve response and survival in cardiac pAL amyloidosis, which necessities further confirmation through a randomized trial. Therefore, we designed a multi-center randomized open-label controlled study to investigate the efficacy and safety of co-administration of oral doxycycline with BCD regimen in treatment-naïve patients with Mayo stage II-III pAL amyloidosis. The primary outcome progression-free survival, and secondary endpoints including overall survival, hematologic response, organ response and toxicity of doxycycline will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old adults.
- •Biopsy proved treatment-naïve pAL amyloidosis.
- •Mayo 2004 stage II-III.
- •dFLC > 50mg/L.
- •Patient must provide informed consent.
排除标准
- •Co-morbidity of uncontrolled infection.
- •Co-morbidity of grade 2 or 3 atrioventricular block.
- •Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia.
- •Co-morbidity of other active malignancy.
- •Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia.
- •Grade 2 or higher neuropathy according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.
- •Allergic history of doxycycline.
- •Neutrophil <1×10E9/L，hemoglobin < 7g/dL，or platelet < 75×10E9/L.
- •Severely compromised hepatic or renal function: ALT or AST > 2.5 × ULN, total bilirubin > 1.5mg/dL，or eGFR < 60mL/min.
研究组 & 干预措施
Doxycycline/BCD chemotherapy
Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Doxycycline (Drug)
Doxycycline/BCD chemotherapy
Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Bortezomib (Drug)
Doxycycline/BCD chemotherapy
Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Cyclophosphamide (Drug)
Doxycycline/BCD chemotherapy
Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Dexamethasone (Drug)
BCD chemotherapy
Bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Bortezomib (Drug)
BCD chemotherapy
Bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Cyclophosphamide (Drug)
BCD chemotherapy
Bortezomib-cyclophosphamide-dexamethasone chemotherapy
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 2 years
The patients are assessed after each cycle of chemotherapy following treatment initiation until progression, relapse, death or study closure at 24-month follow-up.
次要结局
- Overall survival(2 years)
- Hematologic response(2 years)
- Organ response(2 years)
- Adverse events(up to 2 years)
研究者
Jian Li
Professor
Peking Union Medical College Hospital