Clinical trial NCT02207556: Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis Trial
Official title: Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis (DUAL) Trial: A Phase II Open Label Study of Oral Doxycycline Administered as an Adjunct to Plasma Cell Directed Therapy in Light Chain (AL) Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Systemic Amyloidosis
Keywords: AL amyloidosis
amyloidosis
light chain amyloidosis
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2014-08-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study the investigators want to find out more about the addition of the antibiotic, doxycycline, to standard anti-amyloid therapy in people with amyloidosis. The investigators want to find out whether doxycycline improves the response to standard anti-amyloid therapy and whether it causes any problems (side effects).

Detailed description: Organ response to anti-plasma cell therapy in AL amyloidosis tends to lags behind hematologic response as chemotherapy may not clear pre-formed organ amyloid. Doxycycline has been shown to have inhibitory effects on amyloid fibril formation as well as de-fibrillogenic effects and shown to be beneficial in in vitro, murine models and other preclinical studies. The investigators will prospectively evaluate the safety and efficacy of doxycycline in AL amyloidosis patients when used in conjunction with anti-plasma cell chemotherapy.

Eligibility criteria: Inclusion Criteria:

1. Patients with biopsy proven AL amyloidosis.
2. Patients ≥ 18 years of age are eligible.
3. Patient must provide informed consent.
4. All patients must have measurable amyloid organ involvement of a vital organ (eg. heart, liver, kidneys). Localized amyloidosis will also be eligible as long as the amyloid involvement is radiologically measurable.
5. A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
6. Patients who have previously been taking doxycycline will be eligible as long as there is no contraindication to stay on doxycycline 100 mg twice daily (BID) for 1 year in the opinion of the treating physician.
7. Creatinine clearance of \>25 ml/min.

Exclusion Criteria:

1. Patients with severe malabsorption syndrome precluding absorption of oral agents will be excluded.
2. Known intolerance or allergic reactions with doxycycline.
3. Previous chemotherapy for AL amyloidosis.

Primary outcomes:
measure: Hematologic Response
timeFrame: 1 year
Secondary outcomes:
measure: Amyloid Organ Response
timeFrame: 6 months and 1 year
measure: Mortality
timeFrame: Baseline, 3 months, 6 months, 1 year
measure: Patient-reported Health Quality of Life
timeFrame: Baseline, 3, 6, 9 and 12 months
measure: Patient-reported Mental Quality of Life
timeFrame: Baseline, 3, 6, 9 and 12 months
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Anita D'Souza, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: D'Souza A, Szabo A, Flynn KE, Dhakal B, Chhabra S, Pasquini MC, Weihrauch D, Hari PN. Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial. EClinicalMedicine. 2020 Jun 5;23:100361. doi: 10.1016/j.eclinm.2020.100361. eCollection 2020 Jun.