Rationale and design of DUAL study: Doxycycline to Upgrade response in light chain (AL) amyloidosis (DUAL): A phase 2 pilot study of a two-pronged approach of prolonged doxycycline with plasma cell-directed therapy in the treatment of AL amyloidosis. Contemp Clin Trials Commun 2017 Dec;8:33-38
Date
04/27/2018Pubmed ID
29696194Pubmed Central ID
PMC5898504DOI
10.1016/j.conctc.2017.08.012Scopus ID
2-s2.0-85027981960Abstract
Light chain (AL) amyloidosis is a plasma cell neoplasm associated with insoluble fibril deposition from clonal immunoglobulin chains systemically. The disease is associated with high early mortality and morbidity owing to advanced organ deposition as well as lack of proven de-fibrillogenic therapies. Pre-clinical and retrospective clinical data suggests that doxycycline has benefit in AL amyloidosis. The ongoing DUAL study is a single center, open label, phase 2 study in which patients with AL amyloidosis who are undergoing clone-directed therapy for the underlying neoplasm with oral doxycycline given for 1 year to test the hypothesis that prolonged doxycycline use will be safe, feasible, and lead to reduced early mortality in systemic AL amyloidosis and hasten organ amyloid response. Clinical follow up visits will occur at monthly intervals for systemic AL patients and at 3 monthly intervals for localized AL patients. Blood tests will be collected during these time points for hematologic response assessment. Organ testing will be conducted at 3 monthly intervals and radiologic testing will be conducted at 6 monthly intervals. Research blood samples will be collected at baseline, 6 and 12 months. Other correlative studies include matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP) testing and patient-reported outcomes.
Author List
D'Souza A, Flynn K, Chhabra S, Dhakal B, Hamadani M, Jacobsen K, Pasquini M, Weihrauch D, Hari PAuthors
Saurabh Chhabra MD Associate Professor in the Medicine department at Medical College of WisconsinAnita D'Souza MD Associate Professor in the Medicine department at Medical College of Wisconsin
Binod Dhakal MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Kathryn Eve Flynn PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Associate Professor in the Medicine department at Medical College of Wisconsin
