Trial Outcomes & Findings for Doxycycline to Upgrade Organ Response in Light Chain (AL) Amyloidosis Trial (NCT NCT02207556)

NCT ID: NCT02207556

Last Updated: 2021-07-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

1 year

Results posted on

2021-07-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Doxycycline (Localized Disease) 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.	Doxacycline (Systemic Disease) 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.
Overall Study STARTED	7	25
Overall Study COMPLETED	5	20
Overall Study NOT COMPLETED	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Doxycycline (Localized Disease) 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.	Doxacycline (Systemic Disease) 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.
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Death	0	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doxycycline (Localized Disease) n=7 Participants 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 (Systemic Disease) n=25 Participants 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.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	16 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Age, Continuous	61.3 years STANDARD_DEVIATION 10.6 • n=5 Participants	65.5 years STANDARD_DEVIATION 11.4 • n=7 Participants	62.5 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	25 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	21 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	25 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: 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

Outcome measures

Outcome measures
Measure	Doxycycline (Systemic Disease) n=25 Participants 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 (1 Year) 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.
Hematologic Response Complete Response (CR)	6 Participants	—
Hematologic Response Partial Response (PR)	3 Participants	—
Hematologic Response Very Good Partial Response (VGPR)	11 Participants	—
Hematologic Response Expired at 1 year	5 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxycycline (Systemic Disease) n=25 Participants 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 (1 Year) n=25 Participants 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.
Amyloid Organ Response Progressive Disease	8 Participants	3 Participants
Amyloid Organ Response Stable Disease	8 Participants	8 Participants
Amyloid Organ Response Response	6 Participants	9 Participants
Amyloid Organ Response Expired	3 Participants	5 Participants

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Doxycycline (Systemic Disease) n=6 Participants 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 (1 Year) n=25 Participants 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.
Mortality Baseline	6 Participants	25 Participants
Mortality 3 Months	6 Participants	23 Participants
Mortality 6 Months	6 Participants	22 Participants
Mortality 1 Year	6 Participants	20 Participants

SECONDARY outcome

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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Doxycycline (Systemic Disease) n=6 Participants 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 (1 Year) n=25 Participants 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.
Patient-reported Health Quality of Life Baseline	46.1 score on a scale Standard Deviation 9.4	40.9 score on a scale Standard Deviation 0.3
Patient-reported Health Quality of Life 3 Months	51.1 score on a scale Standard Deviation 8.8	40.2 score on a scale Standard Deviation 0.4
Patient-reported Health Quality of Life 6 Months	48.3 score on a scale Standard Deviation 6.3	40.6 score on a scale Standard Deviation 0.4
Patient-reported Health Quality of Life 9 Months	48.9 score on a scale Standard Deviation 8.0	41.7 score on a scale Standard Deviation 0.5
Patient-reported Health Quality of Life 12 Months	49.4 score on a scale Standard Deviation 7.7	44.3 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Doxycycline (Systemic Disease) n=6 Participants 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 (1 Year) n=25 Participants 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.
Patient-reported Mental Quality of Life Baseline	52.1 score on a scale Standard Deviation 10.4	47.9 score on a scale Standard Deviation 0.6
Patient-reported Mental Quality of Life 3 Month	51.4 score on a scale Standard Deviation 10.0	46.0 score on a scale Standard Deviation 0.5
Patient-reported Mental Quality of Life 6 Months	51.2 score on a scale Standard Deviation 9.0	46.4 score on a scale Standard Deviation 0.5
Patient-reported Mental Quality of Life 9 Months	52.6 score on a scale Standard Deviation 11.9	46.7 score on a scale Standard Deviation 0.5
Patient-reported Mental Quality of Life 12 Months	50.7 score on a scale Standard Deviation 10.2	50.6 score on a scale Standard Deviation 0.6

Adverse Events

Doxycycline (Localized Disease)

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Doxycycline (Systemic Disease)

Serious events: 13 serious events

Other events: 24 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Anita D'Souza

Medical College of Wisconsin

Phone: 414-805-0637

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Doxycycline (Localized Disease) n=5 participants at risk 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 (Systemic Disease) n=25 participants at risk 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.
Blood and lymphatic system disorders Lymphocyte production decreased	0.00% 0/5 • 1 year 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.	28.0% 7/25 • Number of events 7 • 1 year 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.
Blood and lymphatic system disorders Neutrophil Count Decreased	0.00% 0/5 • 1 year 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.	24.0% 6/25 • Number of events 6 • 1 year 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.
Blood and lymphatic system disorders Platelet Count Decreased	0.00% 0/5 • 1 year 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.	40.0% 10/25 • Number of events 10 • 1 year 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.
Blood and lymphatic system disorders White Blood Cell Count Decreased	0.00% 0/5 • 1 year 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.	20.0% 5/25 • Number of events 5 • 1 year 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.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Infections and infestations Adenovirus Infection	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Renal and urinary disorders Chronic Kidney Disease	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Cardiac disorders Progressive cardiac amyloidosis	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Blood and lymphatic system disorders Death in Hospice	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Cardiac disorders Natural Death	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Blood and lymphatic system disorders Thrombosis of Vein of Lower Limb	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Hepatobiliary disorders Aspartate Aminotransferase Increased	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Hepatobiliary disorders Alanine Aminotransferase Increased	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Infections and infestations Bacterial Sepsis	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Gastrointestinal disorders Colitis	0.00% 0/5 • 1 year 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.	4.0% 1/25 • Number of events 1 • 1 year 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.
Skin and subcutaneous tissue disorders Drug-Induced Lupus	20.0% 1/5 • Number of events 1 • 1 year 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.	0.00% 0/25 • 1 year 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.