An allocation by random phase II/III trial of doxycycline in comparison to standard therapy in newly-diagnosed cardiac AL amyloidosis patients with bortezomib-based therapy

Phase 1

• Conditions: ight chain (AL) amyloidosis is a protein conformational disease, caused by a small bonemarrow plasma cell clone producing light chains (LCs) that undergo conformational changes,aggregate and deposit in tissues in the form of amyloid fibrils. This process causes dysfunctionof the organs involved and leads to death if not effectively treated.; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2017-002210-31-DE
• Lead Sponsor: Amyloid Center - Biotechnology Research Laboratories Policlinico San Matteo

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-01-24
• Last Update Posted: 9 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

•newly-diagnosed AL amyloidosis
•stage II/IIIa heart involvement
•age >18 years
•planned bortezomib-based therapy
•total bilirubin <1.5 × upper reference limit (url),
•patients with Gilbert disease who have a total bilirubin,
predominantly unconjugated >1.5 × url without any other
liver function test abnormalities are still eligible
•alkaline phosphatase <5 × url
•alanine aminotransferase <3 × url

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

non-AL amyloidosis
· previous treatment for AL amyloidosis
· pregnant or nursing women
· uncontrolled infection
· active malignancy
· known hypersensitivity to doxycycline, bortezomib, boron,
or mannitol
· treatment with drugs potentially affecting doxycycline
absorption
· significant acute gastrointestinal symptoms
· active peptic ulceration and/or esophageal reflux disease
· contraindications to bortezomib based therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The trial aims at establishing whether the addition of the antibiotic<br>doxycycline to anti-plasma cell therapy can reduce early mortality<br>in newly-diagnosed patients with cardiac AL amyloidosis.<br>Cardiac involvement is responsible for almost all the early deaths<br>in AL amyloidosis. Therapy solely aimed at the underlying disease<br>can rescue only a minority of patients with cardiac AL amyloidosis,<br>whose treatment remains a largely unmet need. The severity of<br>cardiac involvement is accurately assessed by a staging system<br>based on cardiac biomarkers. Patients with stage II/IIIa cardiac<br>involvement will be enrolled in this study. ;Secondary Objective: Not applicable;Primary end point(s): proportion surviving at 12 months;Timepoint(s) of evaluation of this end point: 12 months after beginning of the Treatment phase

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): safety, i.e. rate of severe (CTCAE v5.0) grade 3 or greater<br>adverse events)<br>· rate of infective adverse events of any grade<br>· cardiac response (as per consensus criteria) at 2, 4, 6 and 12<br>months<br>· hematologic response (as per consensus criteria) at 2, 4, 6<br>and 12 months<br>· renal response (as per consensus criteria) at 2, 4, 6 and 12<br>months;Timepoint(s) of evaluation of this end point: 12 months after beginning of the Treatment phase