FAM for BOS: Targeted Therapy of Bronchiolitis Obliterans Syndrome

• Sponsor: Stephanie Lee (Other)
• Overall Status: Completed
• CT.gov ID: NCT01307462
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Locations: 11
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving fluticasone propionate, azithromycin, and montelukast sodium (FAM) together works in treating patients with bronchiolitis obliterans who previously underwent stem cell transplant. FAM may be an effective treatment for bronchiolitis obliterans

Condition or Disease	Intervention/Treatment	Phase
Bronchiolitis Obliterans	Drug: fluticasone propionate; Drug: montelukast sodium; Drug: azithromycin	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if the combination treatment of FAM administered in post hematopoietic cell transplantation (HCT) recipients after the diagnosis of new onset bronchiolitis obliterans syndrome (BOS) can decrease the rate of treatment failure relative to an estimated historical rate of 40% using current therapies.

SECONDARY OBJECTIVES:

1. To confirm the safety profile of FAM.

2. To describe the effect on other standard pulmonary function test parameters: forced expiratory flow at 25%-75% of forced vital capacity (FVC) (FEF25-75), residual volume (RV), diffusion capacity of carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1)/FVC ratio and FEV1/slow vital capacity (SVC) ratio with FAM treatment.

3. To determine the change in molecular markers of inflammation and fibrosis in the blood with FAM treatment.

4. To assess the impact of FAM on other chronic graft-versus-host disease (GVHD) manifestations.

5. To assess the impact of FAM on functional status, and health-related quality of life (HRQOL).

6. To describe changes in steroid dosing.

OUTLINE:

Patients receive fluticasone propionate inhaled orally (PO) twice daily (BID), azithromycin PO 3 days a week, and montelukast sodium PO once daily (QD). Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: fluticasone propionate; Given inhaled PO; Other Names: Flonase Flovent ; Drug: montelukast sodium; Given PO; Other Names: Singulair ; Drug: azithromycin; Given PO; Other Names: AzaSite CP 62993 XZ-450

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Failed Treatment [Within 3 months after initiation of study medications]

   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.

Secondary Outcome Measures

1. Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result [From baseline to 6 months]

   National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0)

2. Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO [Baseline and 6 months]

3. Changes in Blood Molecular Markers: IL8 (Azithromycin), Cysteinyl and LTB4 (Monteleukast), and IL1B, TNF, and IL6, as Well as Neutrophil Count (Fluticasone) [Baseline to 6 months]

4. Number of Subjects With Improvements in Other Chronic GVHD Characteristics [Baseline and 3 months]

   Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria.

5. Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50% [Baseline to 6 months]

6. Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36) [Baseline and 6 months]

   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.

7. Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT) [Baseline and 6 months]

   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)

8. Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP) [Baseline and 6 months]

   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.

9. Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale [Baseline and 6 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of BOS after HCT within the 6 months before study enrollment; for this study, BOS is defined as:

• Forced expiratory volume in 1 second (FEV1) < 75% of the predicted normal and FEV1 to slow or inspiratory vital capacity ratio (FEV1/SVC or FEV1/IVC) =< 0.7, both measured before and after administration of bronchodilator OR

• Pathologic diagnosis of BOS demonstrated by lung biopsy

• The baseline absolute FEV1 must be >= 10% lower than the pre-transplant absolute FEV1 as defined by the pre-transplant FEV1 minus the baseline FEV1, both measured before administration of a bronchodilator

• Participant (or parent/guardian) has the ability to understand and willingness to sign a written consent document

Exclusion Criteria:

• Recurrent or progressive malignancy requiring anticancer treatment

• Known history of allergy to or intolerance of montelukast, zafirlukast, azithromycin, erythromycin, or clarithromycin

• Pregnancy or nursing; all females of childbearing potential must have a negative serum or urine pregnancy test < 7 days before study drug administration

• Transaminases > 5 X upper limit of normal (ULN)

• Total bilirubin > 3 X ULN

• Chronic treatment with any inhaled steroid for > 1 month in the past three months

• Treatment with montelukast or zafirlukast for > 1 month during the past three months

• Treatment with prednisone at > 1.2 mg/kg/day (or equivalent steroid)

• Treatment with rifampin or phenobarbital, aspirin at doses > 325 mg/day, or ibuprofen at doses > 1200 mg/day

• Treatment with any Food and Drug Administration (FDA) non approved study medication within the past 4 weeks; off-label treatment with an FDA-approved medication is allowed

• Chronic oxygen therapy

• Evidence of any viral, bacterial or fungal infection involving the lung and not responding to appropriate treatment

• Clinical asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness)

• Any condition that, in the opinion of the enrolling investigator, would interfere with the subject's ability to comply with the study requirements

• Uncontrolled substance abuse or psychiatric disorder

• Inability to perform pulmonary function tests (PFT) reliably, as determined by the enrolling investigator or PFT lab

• Life expectancy < 6 months at the time of enrollment as judged by the enrolling investigator

• Baseline post-bronchodilator FEV1 < 20% of predicted normal before or after albuterol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic - Scottsdale	Scottsdale	Arizona	United States	85054
2	Stanford University	Stanford	California	United States	94305
3	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
4	National Cancer Institute Experimental Transplantation & Immunology Branch	Bethesda	Maryland	United States	20892
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
6	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota	United States	55455
7	Siteman Cancer Center at Washington University	Saint Louis	Missouri	United States	63110
8	Weill Cornell Medical College	New York	New York	United States	10065
9	Vanderbilt University	Nashville	Tennessee	United States	37232
10	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
11	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Stephanie Lee
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stephanie Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
• Study Chair: Kirsten Williams, National Cancer Institute (NCI)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Stephanie Lee, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
• ClinicalTrials.gov Identifier: NCT01307462
• Other Study ID Numbers: 2367.00; NCI-2011-00203; U54CA163438; RDCRN 6503
• First Posted: Mar 3, 2011
• Last Update Posted: Oct 4, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Bronchiolitis; Bronchiolitis Obliterans; Fluticasone; Xhance; Azithromycin; Montelukast

Study Results

Participant Flow

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	36
COMPLETED	35
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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 Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	17 47.2%
Male	19 52.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.8%
Not Hispanic or Latino	35 97.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 5.6%
White	34 94.4%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Failed Treatment
Description	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.
Time Frame	Within 3 months after initiation of study medications

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	36
Count of Participants [Participants]	2 5.6%

2. Secondary Outcome

Title	Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result
Description	National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0)
Time Frame	From baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	36
SAEs attributable to FAM	11 30.6%
Stopped FAM during study	1 2.8%

3. Secondary Outcome

Title	Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	36
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Changes in Blood Molecular Markers: IL8 (Azithromycin), Cysteinyl and LTB4 (Monteleukast), and IL1B, TNF, and IL6, as Well as Neutrophil Count (Fluticasone)
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	0

5. Secondary Outcome

Title	Number of Subjects With Improvements in Other Chronic GVHD Characteristics
Description	Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

33 of 36 participants were evaluable at 3 months due to missing provider survey data

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	33
Count of Participants [Participants]	12 33.3%

6. Secondary Outcome

Title	Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50%
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

24 out of 36 subjects were evaluable at 6mo due to missing data.

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	24
Count of Participants [Participants]	17 47.2%

7. Secondary Outcome

Title	Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

24 of 36 subjects were evaluable at 6mo due to missing patient survey data.

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	24
SF-36 norm-based physical functioning score	0.0
SF-36 norm-based role-physical score	0.0
SF-36 norm-based bodily pain score	0.0
SF-36 norm-based general health score	-2.38
SF-36 norm-based vitality score	1.56
SF-36 norm-based social functioning score	5.45
SF-36 norm-based role-emotional score	0.0
SF-36 norm-based mental health score	0.0
SF-36 standardized physical component score	-1.21
SF-36 standardized mental component score	1.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based physical functioning score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.81
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based role-physical score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.18
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based bodily pain score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.48
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based general health score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.26
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based vitality score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.23
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based social functioning score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.36
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based role-emotional score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.41
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 norm-based mental health score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.80
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 standardized physical component score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.80
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	SF-36 standardized mental component score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.23
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
Description	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)
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

24 of 36 subjects were evaluable at 6mo due to missing patient survey data.

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	24
FACT physical well-being	0.5
FACT social/family well-being	-1
FACT emotional well-being	0
FACT functional well-being	1
FACT BMT subscale	-0.78
FACT trial outcome index	2
FACT-G	2.5
FACT-BMT total	2.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT physical well-being
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT social/family well-being
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT emotional well-being
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT functional well-being
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT BMT subscale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.84
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT trial outcome index
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT-G
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.71
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	FACT-BMT total
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.54
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

24 of 36 subjects were evaluable at 6mo due to missing patient survey data.

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	24
HAP MAS	0.5
HAP AAS	4.5
Modified HAP AAS	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	HAP maximum activity score - highest item still doing
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.37
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	HAP adjusted activity score - MAS minus stopped
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.39
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Modified HAP adjusted activity score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.39
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
Description	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.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

24 of 36 subjects were evaluable at 6mo due to missing patient survey data.

Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
Measure Participants	24
LSS skin scale	-5.63
LSS energy scale	-7.14
LSS lung scale	-5
LSS eye scale	-8.33
LSS nutrition scale	0
LSS psychological scale	0
LSS mouth scale	0
LSS overall summary scale	-7.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom skin scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.11
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom energy scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.007
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom lung scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.20
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom eye scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.002
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom nutrition scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.52
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom psychological scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.22
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom mouth scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.002
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Treatment (BOS Therapy)
	Comments	Lee symptom overall summary scale
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	Treatment (BOS Therapy)
Arm/Group Description	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.
All Cause Mortality
	Treatment (BOS Therapy)
	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)
Serious Adverse Events
	Treatment (BOS Therapy)
	Affected / at Risk (%)	# Events
Total	24/36 (66.7%)
Blood and lymphatic system disorders
Neutropenia	1/36 (2.8%)	1
Leukocytosis	1/36 (2.8%)	1
General disorders
Edema limbs	1/36 (2.8%)	1
Fever	1/36 (2.8%)	1
Infections and infestations
Sepsis	1/36 (2.8%)	1
Metabolism and nutrition disorders
Hyperglycemia	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Pain	2/36 (5.6%)	2
Nervous system disorders
Presyncope	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary nodules	1/36 (2.8%)	1
Hypoxia	1/36 (2.8%)	1
Pneumonia	3/36 (8.3%)	3
Pneumonitis	1/36 (2.8%)	1
Fluid overload	1/36 (2.8%)	1
Lung infection	3/36 (8.3%)	3
Dyspnea	3/36 (8.3%)	4
Pulmonary Embolus	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment (BOS Therapy)
	Affected / at Risk (%)	# Events
Total	9/36 (25%)
Cardiac disorders
Ventricular tachycardia	1/36 (2.8%)	1
General disorders
Edema	1/36 (2.8%)	1
Investigations
Alanine aminotransferase increased	1/36 (2.8%)	1
Thrombocytopenia	1/36 (2.8%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Cavitary Pulmonary Lesion	1/36 (2.8%)	1
Lung infection	1/36 (2.8%)	1
Skin and subcutaneous tissue disorders
Rash maculopapular	1/36 (2.8%)	1
Vascular disorders
Hypertension	1/36 (2.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.