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

Not Applicable

Completed

• Conditions: Amyloidosis; Systemic
• Interventions: Drug: Doxycycline; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone

• Registration Number: NCT03401372
• Lead Sponsor: Jian Li

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-09
• Study First Submitted QC: 2018-01-16
• Study First Posted: 2018-01-17
• Study Start: 2018-04-21
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-19
• Last Update Posted: 2021-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Doxycycline/BCD chemotherapy	Cyclophosphamide	Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
Doxycycline/BCD chemotherapy	Dexamethasone	Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
Doxycycline/BCD chemotherapy	Doxycycline	Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
Doxycycline/BCD chemotherapy	Bortezomib	Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
BCD chemotherapy	Bortezomib	Bortezomib-cyclophosphamide-dexamethasone chemotherapy
BCD chemotherapy	Cyclophosphamide	Bortezomib-cyclophosphamide-dexamethasone chemotherapy
BCD chemotherapy	Dexamethasone	Bortezomib-cyclophosphamide-dexamethasone chemotherapy

Primary Outcome Measures

Name	Time	Method
Progression-free survival	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival	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. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure.
Hematologic response	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. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure.
Organ response	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. If the primary endpoint has reached, patients will also be followed up every 3 months thereafter until death or study closure.
Adverse events	up to 2 years	Adverse events are collected until 30 days after last dose of doxycycline.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China