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

February 19, 2021 updated by: Jian Li

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100730
        • Peking Union Medical College Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Doxycycline/BCD chemotherapy
Doxycycline combined with bortezomib-cyclophosphamide-dexamethasone chemotherapy
Drug: Doxycycline
Oral doxycycline 100mg twice daily
Drug: Bortezomib
1.3mg/m2 of bortezomib on days 1, 8, 15 and 22 of a 35-day cycle
Drug: Cyclophosphamide
300mg/m2 cyclophosphamide on days 1, 8, 15 and 22 of a 35-day cycle
Drug: Dexamethasone
40mg of dexamethasone on days 1, 8, 15 and 22 of a 35-day cycle
Active Comparator: BCD chemotherapy
Bortezomib-cyclophosphamide-dexamethasone chemotherapy
Drug: Bortezomib
1.3mg/m2 of bortezomib on days 1, 8, 15 and 22 of a 35-day cycle
Drug: Cyclophosphamide
300mg/m2 cyclophosphamide on days 1, 8, 15 and 22 of a 35-day cycle
Drug: Dexamethasone
40mg of dexamethasone on days 1, 8, 15 and 22 of a 35-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 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.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 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.
2 years
Hematologic response
Time Frame: 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.
2 years
Organ response
Time Frame: 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.
2 years
Adverse events
Time Frame: up to 2 years
Adverse events are collected until 30 days after last dose of doxycycline.
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jian Li

Collaborators

Peking University First Hospital
Tongji Hospital
Nanfang Hospital of Southern Medical University
Beijing Chao Yang Hospital
Beijing Anzhen Hospital
Shanghai Changzheng Hospital
West China Hospital Affiliated with Sichuan University
Union Hospital Affiliated with Tongji Medical College of HUST

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 21, 2018

Primary Completion (Actual)

December 31, 2020

Study Completion (Actual)

December 31, 2020

Study Registration Dates

First Submitted

January 9, 2018

First Submitted That Met QC Criteria

January 16, 2018

First Posted (Actual)

January 17, 2018

Study Record Updates

Last Update Posted (Actual)

February 23, 2021

Last Update Submitted That Met QC Criteria

February 19, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PUMCH-AL2017

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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