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Primary Systemic AmyloidosisPhase 2DUALNCT02207556

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

A Phase 2 study testing Doxycycline in people with Primary Systemic Amyloidosis, run by Medical College of Wisconsin at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Primary Systemic Amyloidosis
What is being tested?
Doxycycline
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
1 Oct 2014to 19 May 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Froedtert & Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

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

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).

Read the 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.

Being tested
Doxycycline
Keywords
AL amyloidosis, amyloidosis, light chain amyloidosis
Medical subject headings
Immunoglobulin Light-chain Amyloidosis, Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DoxycyclineDrug

    Also called Doxycycline monohydrate

    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.
Study groups in NCT02207556
Study groupRoleWhat they receive
DoxycyclineExperimentalDoxycycline will be administered at dose of 100mg orally twice daily for 1 year.
Receives: Drug: Doxycycline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 year

Secondary outcomes (4)

  1. 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.

    Measured: 6 months and 1 year

  2. Mortality

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

    Measured: Baseline, 3 months, 6 months, 1 year

  3. 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.

    Measured: Baseline, 3, 6, 9 and 12 months

  4. 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.

    Measured: Baseline, 3, 6, 9 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2014 (estimated)
  2. Study start1 Oct 2014
  3. Primary completion31 Jul 2017
  4. Study completion19 May 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02207556
Sponsor's protocol ID
22850
Other IDs
KL2TR001438, K23HL141445, 86-004-26
Acronym
DUAL
Status last verified
Jun 2021
First submitted
23 Jul 2014
Last updated
9 Jul 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32529175

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxycycline in people with Primary Systemic Amyloidosis, run by Medical College of Wisconsin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hematologic Response (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02207556, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2021.

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