Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis Trial

Primary Systemic Amyloidosis Clinical Trial

— DUAL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02207556
• Other study ID #: 22850
• Secondary ID: KL2TR001438K23HL
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2014
• Est. completion date: May 19, 2020

Study information

• Verified date: June 2021
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 19, 2020
• Est. primary completion date: July 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis
• Primary Systemic Amyloidosis

Intervention

Drug:
• Doxycycline
Doxycycline will be continued until one of the following criteria is met: Patient has completed 1 year of doxycycline therapy Patient develops any grade 3-4 toxicity related to doxycycline use.

Locations

Country	Name	City	State
United States	Froedtert & Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Medical College of Wisconsin	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematologic Response	This measure will record the number of subjects for each grade of response to therapy for subjects with Systematic Disease (hematologic) only. Hematologic response will be determined as follows.; Complete response (CR) - Negative serum/urine immunofixation with normal Free Light Chain (FLC) ratio; Very Good Partial Response (VGPR)- Difference between involved and uninvolved FLCs (dFLC) < 40 mg/L; Partial Response (PR)- dFLC decrease > 50%; No Response (NR)- less then PR.	1 year
Secondary	Amyloid Organ Response	This measure is the number of subjects (systemic disease only) for each grade of response. Efficacy will be measured in heart, liver, or kidney.; Heart N-terminal (NT)-proBNP response >30% and > 300 ng/L decrease in patients with baseline NT-proBNP =650 ng/L (Patients with progressively worsening renal function cannot be scored for NT-proBNP progression).; Improvement by 2 New York Heart Association (NYHA) classes without an increase in diuretic use or in echocardiographic wall thickness = 2 mm reduction in the interventricular septal thickness by echocardiogram or improvement of ejection fraction by =20%.; Liver; =50% decrease in an initially elevated alkaline phosphatase level, or Decrease in liver size by at least 2 cm by ultrasound.; Kidney 50% reduction in 24-hour urine protein excretion (at least 0.5 g/day) without worsening of creatinine or creatinine clearance by 25% over baseline.; Soft Tissue RECIST criteria will be used.	6 months and 1 year
Secondary	Mortality	The number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year	Baseline, 3 months, 6 months, 1 year
Secondary	Patient-reported Health Quality of Life	Subjects will complete the Patient Reported Outcomes Measurement Information System Global Health instrument, a 10-item standardized patient-reported outcome measure that provides global ratings of physical function, fatigue, pain, emotional distress to report on common domains of health-related quality of life. The survey comprises a series of 5-response Likert-style questions. For each question, a low score indicates lesser or absent symptom or condition and higher indicates more severe symptom or condition (e.g., 1= None to 5=Very severe). Automated scoring produces a T-score for each domain. This measure reports the physical health score. T-scores for this domain range from 16.2 to 67.7. Higher scores indicate poorer physical health.	Baseline, 3, 6, 9 and 12 months
Secondary	Patient-reported Mental Quality of Life	Subjects will complete the Patient Reported Outcomes Measurement Information System Global Health instrument, a 10-item standardized patient-reported outcome measure that provides global ratings of physical function, fatigue, pain, emotional distress to report on common domains of health-related quality of life. The survey comprises a series of 5-response Likert-style questions. For each question, a low score indicates lesser or absent symptom or condition and higher indicates more severe symptom or condition (e.g., 1= None to 5=Very severe). Automated scoring produces a T-score for each domain. This measure reports the mental health score. T-scores for this domain range from 21.2 to 67.6. Higher scores indicate poorer mental health.	Baseline, 3, 6, 9 and 12 months