BCD With or Without Doxycycline in Mayo Stage II-III Light Chain Amyloidosis Patients

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

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.

Inclusion Criteria:

• ≥18 years old adults.
• Biopsy proved treatment-naïve pAL amyloidosis.
• Mayo 2004 stage II-III.
• dFLC > 50mg/L.
• Patient must provide informed consent.

Exclusion Criteria:

• 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 3.0.
• 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.