Nutritional and Metabolic Diseases

All Conditions

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Paraproteinemias

AL Amyloidosis

Anti-Infective Agents

All Drugs and Chemicals

Doxycycline

Anti-Bacterial Agents

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Doxycycline will be administered at dose of 100mg orally twice daily for 1 year.

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.

Anita D'Souza, MD

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).

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.

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

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

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.

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.

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

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.

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.

National Heart, Lung, and Blood Institute (NHLBI)

Medical College of Wisconsin

Assistant Professor

Grade was determined using the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Events graded as 4 or 5 were considered serious regardless of the standard criteria.

Doxycycline will be administered at dose of 100mg orally twice daily for 1 year.

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.

Doxycycline (Localized Disease)

Doxycycline (Systemic Disease)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Two subjects in the Localized Disease arm signed consent, but did not proceed to the treatment phase of the study. One subject withdrew consent and one subject was determined to be ineligible and was withdrawn by the investigator. Baseline demographic data were collected for these subjects.

Dr. Anita D'Souza

Hematologic response is not relevant to subjects with localized disease. Subjects with localized disease were not included in this analysis. Five participants had expired by the 1 year time point

Hematologic Response

Progressive Disease

Stable Disease

Response

Expired

Doxycycline (6 Months)

Doxycycline (1 Year)

Amyloid Organ Response

Baseline

3 Months

6 Months

1 Year

Doxacycline (Systemic Disease)

Mortality

9 Months

12 Months

One subject in the Localized cohort withdrew consent prior to the 6-month visit. Five subjects in the Systemic Disease cohort expired during the course of the study; two subjects came off study; and one was lost to follow-up.

Patient-reported Health Quality of Life

3 Month

Patient-reported Mental Quality of Life

Overall Study

Spots Global Cancer Trial Database for Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis Trial

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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