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

Jian Li

Status: Completed

Conditions: Amyloidosis; Systemic

Treatments: Drug: Bortezomib; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Doxycycline

Study type: Interventional

Funder types: Other

Identifiers

NCT03401372

PUMCH-AL2017

Details and patient eligibility

About

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.

Enrollment: 140 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

Doxycycline/BCD chemotherapy

Experimental group

Description:

Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy

Treatment:

Drug: Dexamethasone

Drug: Cyclophosphamide

Drug: Doxycycline

Drug: Bortezomib

BCD chemotherapy

Active Comparator group

Description:

Bortezomib-cyclophosphamide-dexamethasone chemotherapy

Treatment:

Drug: Dexamethasone

Drug: Cyclophosphamide

Drug: Bortezomib