Trial Outcomes & Findings for Targeted Therapy of Bronchiolitis Obliterans Syndrome (NCT NCT01307462)
NCT ID: NCT01307462
Last Updated: 2017-10-04
Results Overview
Treatment failure is defined as sustained, absolute decrease (worsening) of the FEV1 by \>= 10% predicted in comparison to the baseline FEV1. Must be confirmed by a second PFT 2 weeks after the first measurement.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Within 3 months after initiation of study medications
Results posted on
2017-10-04
Participant Flow
Participant milestones
| Measure |
Treatment (BOS Therapy)
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
COMPLETED
|
35
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Targeted Therapy of Bronchiolitis Obliterans Syndrome
Baseline characteristics by cohort
| Measure |
Treatment (BOS Therapy)
n=36 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
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Age, Continuous
|
57 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within 3 months after initiation of study medicationsTreatment failure is defined as sustained, absolute decrease (worsening) of the FEV1 by \>= 10% predicted in comparison to the baseline FEV1. Must be confirmed by a second PFT 2 weeks after the first measurement.
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=36 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
|
Number of Subjects Who Failed Treatment
|
2 Participants
|
SECONDARY outcome
Timeframe: From baseline to 6 monthsNational Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0)
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=36 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
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Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result
SAEs attributable to FAM
|
11 Participants
|
|
Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result
Stopped FAM during study
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsOutcome measures
| Measure |
Treatment (BOS Therapy)
n=36 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsPopulation: Data were not collected
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and 3 monthsPopulation: 33 of 36 participants were evaluable at 3 months due to missing provider survey data
Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria.
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=33 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
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Number of Subjects With Improvements in Other Chronic GVHD Characteristics
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsPopulation: 24 out of 36 subjects were evaluable at 6mo due to missing data.
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=24 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
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Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50%
|
17 Participants
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsPopulation: 24 of 36 subjects were evaluable at 6mo due to missing patient survey data.
SF-36 subscales have min=0 and max=100; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome.
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=24 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|
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Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based physical functioning score
|
0.0 units on a scale
Interval -23.15 to 14.73
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|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based role-physical score
|
0.0 units on a scale
Interval -17.14 to 39.18
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based bodily pain score
|
0.0 units on a scale
Interval -13.52 to 17.33
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based general health score
|
-2.38 units on a scale
Interval -20.02 to 17.64
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|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based vitality score
|
1.56 units on a scale
Interval -15.61 to 21.85
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based social functioning score
|
5.45 units on a scale
Interval -27.27 to 38.18
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based role-emotional score
|
0.0 units on a scale
Interval -23.32 to 23.32
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 norm-based mental health score
|
0.0 units on a scale
Interval -11.26 to 16.9
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 standardized physical component score
|
-1.21 units on a scale
Interval -21.65 to 25.16
|
|
Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
SF-36 standardized mental component score
|
1.64 units on a scale
Interval -21.63 to 25.76
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsPopulation: 24 of 36 subjects were evaluable at 6mo due to missing patient survey data.
FACT-BMT subscales have various min/max, see below; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome. FACT physical well-being (0-28) FACT social/family well-being (0-28) FACT emotional well-being (0-24) FACT functional well-being (0-28) FACT Bone Marrow Transplant (BMT) subscale (0-40) FACT trial outcome index (0-96) FACT-General (G) (0-108) FACT-BMT total (0-148)
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=24 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT physical well-being
|
0.5 units on a scale
Interval -8.0 to 12.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT social/family well-being
|
-1 units on a scale
Interval -6.83 to 7.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT emotional well-being
|
0 units on a scale
Interval -6.0 to 17.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT functional well-being
|
1 units on a scale
Interval -15.0 to 13.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT BMT subscale
|
-0.78 units on a scale
Interval -7.0 to 10.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT trial outcome index
|
2 units on a scale
Interval -30.0 to 22.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT-G
|
2.5 units on a scale
Interval -23.0 to 23.67
|
|
Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT-BMT total
|
2.17 units on a scale
Interval -30.0 to 25.0
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SECONDARY outcome
Timeframe: Baseline and 6 monthsPopulation: 24 of 36 subjects were evaluable at 6mo due to missing patient survey data.
HAP subscales have min=0 and max=94; results are given as change in 6mo score compared to baseline score, not actual score, and a positive change is correlated with improvement in clinical outcome. Maximum Activity Score (MAS) is highest item number answered still doing. Represents highest oxygen demanding activity that respondent still performs. Adjusted Activity Score (AAS) is MAS minus total number of stopped doing responses below MAS. A measure of usual daily activities. Modified AAS is MAS minus total number of stopped doing responses below MAS but not penalized for not doing activities not permitted post transplant. The following items are not counted against the score:11,15,19,20,22,25,34,41,42,47,49,50,52,53,54,57,72,73,77,78.
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=24 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
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Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
HAP MAS
|
0.5 units on a scale
Interval -41.0 to 30.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
HAP AAS
|
4.5 units on a scale
Interval -49.0 to 42.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
Modified HAP AAS
|
3.5 units on a scale
Interval -46.0 to 36.0
|
SECONDARY outcome
Timeframe: Baseline and 6 monthsPopulation: 24 of 36 subjects were evaluable at 6mo due to missing patient survey data.
Lee symptom scale (LSS) has subscales with min=0, max=100; results are given as change in 6mo score compared to baseline score, not actual score, and a negative change is correlated with improvement in clinical outcome.
Outcome measures
| Measure |
Treatment (BOS Therapy)
n=24 Participants
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
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|---|---|
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Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS skin scale
|
-5.63 units on a scale
Interval -45.0 to 50.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS energy scale
|
-7.14 units on a scale
Interval -39.29 to 14.29
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS lung scale
|
-5 units on a scale
Interval -55.0 to 45.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS eye scale
|
-8.33 units on a scale
Interval -66.67 to 8.33
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS nutrition scale
|
0 units on a scale
Interval -30.0 to 10.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS psychological scale
|
0 units on a scale
Interval -50.0 to 50.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS mouth scale
|
0 units on a scale
Interval -75.0 to 0.0
|
|
Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
LSS overall summary scale
|
-7.77 units on a scale
Interval -32.21 to 2.52
|
Adverse Events
Treatment (BOS Therapy)
Serious events: 24 serious events
Other events: 9 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Treatment (BOS Therapy)
n=36 participants at risk
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|
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General disorders
Edema limbs
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary nodules
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
General disorders
Fever
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Nervous system disorders
Presyncope
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
8.3%
3/36 • Number of events 3 • 6 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain
|
5.6%
2/36 • Number of events 2 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Fluid overload
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
8.3%
3/36 • Number of events 3 • 6 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.6%
2/36 • Number of events 2 • 6 months
|
|
Infections and infestations
Sepsis
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
3/36 • Number of events 4 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolus
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.8%
1/36 • Number of events 1 • 6 months
|
Other adverse events
| Measure |
Treatment (BOS Therapy)
n=36 participants at risk
Patients receive fluticasone propionate inhaled PO BID, azithromycin PO 3 days a week, and montelukast sodium PO QD. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cavitary Pulmonary Lesion
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
General disorders
Edema
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Investigations
Alanine aminotransferase increased
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Vascular disorders
Hypertension
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Skin and subcutaneous tissue disorders
Rash maculopapular
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Investigations
Thrombocytopenia
|
2.8%
1/36 • Number of events 1 • 6 months
|
|
Cardiac disorders
Ventricular tachycardia
|
2.8%
1/36 • Number of events 1 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place