A Phase 2 interventional study of Doxycycline in Primary Systemic Amyloidosis, sponsored by Medical College of Wisconsin. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-09.
Sponsored by Medical College of Wisconsin · Phase 2, Interventional, and Treatment
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.
167 studies on the registry are indexed under Immunoglobulin Light-chain Amyloidosis; 57 are open to participants now.
This study's enrollment of 32 is below the median of 37 across 120 interventional studies indexed under Immunoglobulin Light-chain Amyloidosis.
Browse Immunoglobulin Light-chain Amyloidosis studies →Medical College of Wisconsin is the lead sponsor of 540 studies on the registry; 120 are open to participants now.
Of its 71 completed or terminated interventional studies of FDA-regulated products, 56 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Doxycycline will be administered at dose of 100mg orally twice daily for 1 year.
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.
Also known as: Doxycycline monohydrate
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.
Time frame: 1 year
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.
Time frame: 6 months and 1 year
Mortality
The number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year
Time frame: Baseline, 3 months, 6 months, 1 year
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.
Time frame: Baseline, 3, 6, 9 and 12 months
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.
Time frame: Baseline, 3, 6, 9 and 12 months
Subjects were stratified by the type of amyloidosis. Subjects with primarily organ-based disease were classified as Localized Disease), whereas subjects with hematologic disease were classified as Systematic Disease. Each population received the same intervention but assessment of the clinical outcomes used different classification categories.
| Milestone | Doxycycline (Localized Disease) | Doxacycline (Systemic Disease) |
|---|---|---|
| Started | 7 | 25 |
| Completed | 5 | 20 |
| Not completed | 2 | 5 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Death | 0 | 5 |
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.
| Participants | Doxycycline (Systemic Disease) |
|---|---|
| Complete Response (CR) | 6 |
| Partial Response (PR) | 3 |
| Very Good Partial Response (VGPR) | 11 |
| Expired at 1 year | 5 |
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.
| Participants | Doxycycline (6 Months) | Doxycycline (1 Year) |
|---|---|---|
| Progressive Disease | 8 | 3 |
| Stable Disease | 8 | 8 |
| Response | 6 | 9 |
| Expired | 3 | 5 |
The number of living subjects will be determined at Baseline, 3 months, 6 months and 1 year
| Participants | Doxycycline (Localized Disease) | Doxacycline (Systemic Disease) |
|---|---|---|
| Baseline | 6 | 25 |
| 3 Months | 6 | 23 |
| 6 Months | 6 | 22 |
| 1 Year | 6 | 20 |
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.
| score on a scale | Doxycycline (Localized Disease) | Doxacycline (Systemic Disease) |
|---|---|---|
| Baseline | 46.1 ± 9.4 | 40.9 ± 0.3 |
| 3 Months | 51.1 ± 8.8 | 40.2 ± 0.4 |
| 6 Months | 48.3 ± 6.3 | 40.6 ± 0.4 |
| 9 Months | 48.9 ± 8.0 | 41.7 ± 0.5 |
| 12 Months | 49.4 ± 7.7 | 44.3 ± 0.4 |
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.
| score on a scale | Doxycycline (Localized Disease) | Doxacycline (Systemic Disease) |
|---|---|---|
| Baseline | 52.1 ± 10.4 | 47.9 ± 0.6 |
| 3 Month | 51.4 ± 10.0 | 46.0 ± 0.5 |
| 6 Months | 51.2 ± 9.0 | 46.4 ± 0.5 |
| 9 Months | 52.6 ± 11.9 | 46.7 ± 0.5 |
| 12 Months | 50.7 ± 10.2 | 50.6 ± 0.6 |
Collected over 1 year. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Doxycycline (Localized Disease) | 0/5 (0%) | 1/5 (20%) | 5/5 (100%) |
| Doxycycline (Systemic Disease) | 5/25 (20%) | 13/25 (52%) | 24/25 (96%) |
| Event | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) |
|---|---|---|
| Platelet Count DecreasedBlood and lymphatic system disorders | 0/5 | 10/25 |
| Lymphocyte production decreasedBlood and lymphatic system disorders | 0/5 | 7/25 |
| Neutrophil Count DecreasedBlood and lymphatic system disorders | 0/5 | 6/25 |
| White Blood Cell Count DecreasedBlood and lymphatic system disorders | 0/5 | 5/25 |
| Drug-Induced LupusSkin and subcutaneous tissue disorders | 1/5 | 0/25 |
| HyperuricemiaMetabolism and nutrition disorders | 0/5 | 1/25 |
| Adenovirus InfectionInfections and infestations | 0/5 | 1/25 |
| Chronic Kidney DiseaseRenal and urinary disorders | 0/5 | 1/25 |
| Progressive cardiac amyloidosisCardiac disorders | 0/5 | 1/25 |
| Death in HospiceBlood and lymphatic system disorders | 0/5 | 1/25 |
| Event | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) |
|---|---|---|
| HyperglycemiaInvestigations | 2/5 | 17/25 |
| HyponatremiaInvestigations | 2/5 | 16/25 |
| Weight LossInvestigations | 1/5 | 16/25 |
| FatigueGeneral disorders | 3/5 | 15/25 |
| HypertensionVascular disorders | 3/5 | 6/25 |
| Edema, LimbGeneral disorders | 2/5 | 15/25 |
| DiarrheaGastrointestinal disorders | 1/5 | 15/25 |
| HypoalbuminemiaInvestigations | 1/5 | 15/25 |
| AnemiaBlood and lymphatic system disorders | 0/5 | 15/25 |
| DizzinessNervous system disorders | 0/5 | 15/25 |
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.
| Age, Categorical(Participants) | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 3 | 16 | 19 |
| >=65 years | 4 | 9 | 13 |
| Age, Continuous(years) | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) | Total |
|---|---|---|---|
| Mean | 61.3 ± 10.6 | 65.5 ± 11.4 | 62.5 ± 10.5 |
| Sex: Female, Male(Participants) | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) | Total |
|---|---|---|---|
| Female | 5 | 9 | 14 |
| Male | 2 | 16 | 18 |
| Ethnicity (NIH/OMB)(Participants) | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 7 | 25 | 32 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 4 | 4 |
| White | 7 | 21 | 28 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Doxycycline (Localized Disease) | Doxycycline (Systemic Disease) | Total |
|---|---|---|---|
| United States | 7 | 25 | 32 |
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Immunoglobulin Light-chain Amyloidosis→
Medical College of Wisconsin