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NCT Number: NCT02207556

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

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).

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Key information

Conditions

Primary Systemic Amyloidosis Amyloidosis Immune System Diseases Immunoglobulin Light-chain Amyloidosis Immunoproliferative Disorders Lymphoproliferative Disorders Metabolic Diseases Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Nutritional and Metabolic Diseases Paraproteinemias Proteostasis Deficiencies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with biopsy proven AL amyloidosis.
  • Patients ≥ 18 years of age are eligible.
  • Patient must provide informed consent.
  • 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.
  • A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
  • 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.
  • Creatinine clearance of >25 ml/min.

Exclusion criteria

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

Treatment and study plan

Doxycycline

Drug

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.

Other names: Doxycycline monohydrate

Primary outcomes

  1. Hematologic Response

    Time frame: 1 year

    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.

Secondary outcomes

  1. Amyloid Organ Response

    Time frame: 6 months and 1 year

    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.

  2. Mortality

    Time frame: Baseline, 3 months, 6 months, 1 year

    The number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year

  3. Patient-reported Health Quality of Life

    Time frame: Baseline, 3, 6, 9 and 12 months

    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.

  4. Patient-reported Mental Quality of Life

    Time frame: Baseline, 3, 6, 9 and 12 months

    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.

Sponsors and collaborators

Lead sponsor

Medical College of Wisconsin

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study 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

Acronym: DUAL

Important dates

Study start
2014
Primary completion
2017
Study completion
2020
First posted
Aug 4, 2014
Registry last updated
Jul 9, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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