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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-00203 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| U54CA163438 | U.S. NIH Grant/Contract | View source | |
| RDCRN 6503 | Other Identifier | DMCC |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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
PRIMARY OBJECTIVES:
I. 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:
I. To confirm the safety profile of FAM.
II. 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.
III. To determine the change in molecular markers of inflammation and fibrosis in the blood with FAM treatment.
IV. To assess the impact of FAM on other chronic graft-versus-host disease (GVHD) manifestations.
V. To assess the impact of FAM on functional status, and health-related quality of life (HRQOL).
VI. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (BOS therapy) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fluticasone propionate | Drug | Given inhaled PO |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Who Failed Treatment | 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. | Within 3 months after initiation of study medications |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result | National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0) | From baseline to 6 months |
| Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO |
Not provided
Inclusion Criteria:
Diagnosis of BOS after HCT within the 6 months before study enrollment; for this study, BOS is defined as:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Stephanie Lee | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Kirsten Williams | National Cancer Institute (NCI) | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic - Scottsdale | Scottsdale | Arizona | 85054 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26475726 | Result | Williams KM, Cheng GS, Pusic I, Jagasia M, Burns L, Ho VT, Pidala J, Palmer J, Johnston L, Mayer S, Chien JW, Jacobsohn DA, Pavletic SZ, Martin PJ, Storer BE, Inamoto Y, Chai X, Flowers MED, Lee SJ. Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016 Apr;22(4):710-716. doi: 10.1016/j.bbmt.2015.10.009. Epub 2015 Oct 22. | |
| 34126278 | Derived |
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De-identified data are reported in aggregate.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects Who Failed Treatment | 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. | Posted | Count of Participants | Participants | Within 3 months after initiation of study medications |
|
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Edema limbs | General disorders | SNOMED CT | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cavitary Pulmonary Lesion | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Guang-Shing Cheng MD | FHCRC | 206-667-7074 | gcheng2@fhcrc.org |
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| ID | Term |
|---|---|
| D001989 | Bronchiolitis Obliterans |
| ID | Term |
|---|---|
| D001988 | Bronchiolitis |
| D001991 | Bronchitis |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000068298 | Fluticasone |
| C093875 | montelukast |
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| montelukast sodium | Drug | Given PO |
|
|
| azithromycin | Drug | Given PO |
|
|
| Baseline and 6 months |
| 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 |
| Number of Subjects With Improvements in Other Chronic GVHD Characteristics | Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria. | Baseline and 3 months |
| Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50% | Baseline to 6 months |
| Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36) | 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. | Baseline and 6 months |
| Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT) | 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) | Baseline and 6 months |
| Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP) | 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. | Baseline and 6 months |
| Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale | 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. | Baseline and 6 months |
| Stanford |
| California |
| 94305 |
| United States |
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| National Cancer Institute Experimental Transplantation & Immunology Branch | Bethesda | Maryland | 20892 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Siteman Cancer Center at Washington University | St Louis | Missouri | 63110 | United States |
| Weill Cornell Medical College | New York | New York | 10065 | United States |
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Inamoto Y, Martin PJ, Onstad LE, Cheng GS, Williams KM, Pusic I, Ho VT, Arora M, Pidala J, Flowers MED, Gooley TA, Lawler RL, Hansen JA, Lee SJ. Relevance of Plasma Matrix Metalloproteinase-9 for Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021 Sep;27(9):759.e1-759.e8. doi: 10.1016/j.jtct.2021.06.006. Epub 2021 Jun 12. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Participants |
|
|
| Secondary | Number of Subjects Who Experienced Grade 3-5 SAEs Attributable to FAM and Number of Subjects Who Stopped FAM as a Result | National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) (v4.0) | Posted | Count of Participants | Participants | From baseline to 6 months |
|
|
|
| Secondary | Number of Subjects Who Experienced Statistically Significant Changes in FVC, TLC, RV, DLCO | Posted | Count of Participants | Participants | Baseline and 6 months |
|
|
|
| Secondary | Changes in Blood Molecular Markers: IL8 (Azithromycin), Cysteinyl and LTB4 (Monteleukast), and IL1B, TNF, and IL6, as Well as Neutrophil Count (Fluticasone) | Data were not collected | Posted | Baseline to 6 months |
|
|
| Secondary | Number of Subjects With Improvements in Other Chronic GVHD Characteristics | Only includes subjects who had complete or partial response according to the National Institute of Health (NIH) consensus criteria. | 33 of 36 participants were evaluable at 3 months due to missing provider survey data | Posted | Count of Participants | Participants | Baseline and 3 months |
|
|
|
| Secondary | Number of Subjects Were Able to Reduce Their Systemic Steroid Exposure by >=50% | 24 out of 36 subjects were evaluable at 6mo due to missing data. | Posted | Count of Participants | Participants | Baseline to 6 months |
|
|
|
| Secondary | Changes in Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36) | 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. | 24 of 36 subjects were evaluable at 6mo due to missing patient survey data. | Posted | Median | Full Range | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Changes in Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT) | 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) | 24 of 36 subjects were evaluable at 6mo due to missing patient survey data. | Posted | Median | Full Range | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Changes in Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP) | 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. | 24 of 36 subjects were evaluable at 6mo due to missing patient survey data. | Posted | Median | Full Range | units on a scale | Baseline and 6 months |
|
|
|
|
| Secondary | Changes in Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale | 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. | 24 of 36 subjects were evaluable at 6mo due to missing patient survey data. | Posted | Median | Full Range | units on a scale | Baseline and 6 months |
|
|
|
|
| 1 |
| 36 |
| 24 |
| 36 |
| 9 |
| 36 |
| Pulmonary nodules | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Fever | General disorders | SNOMED CT | Systematic Assessment |
|
| Presyncope | Nervous system disorders | SNOMED CT | Systematic Assessment |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | SNOMED CT | Systematic Assessment |
|
| Pain | Musculoskeletal and connective tissue disorders | SNOMED CT | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Fluid overload | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Lung infection | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | SNOMED CT | Systematic Assessment |
|
| Sepsis | Infections and infestations | SNOMED CT | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Pulmonary Embolus | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | SNOMED CT | Systematic Assessment |
|
| Edema | General disorders | SNOMED CT | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | SNOMED CT | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | SNOMED CT | Systematic Assessment |
|
| Hypertension | Vascular disorders | SNOMED CT | Systematic Assessment |
|
| Lung infection | Respiratory, thoracic and mediastinal disorders | SNOMED CT | Systematic Assessment |
|
| Rash maculopapular | Skin and subcutaneous tissue disorders | SNOMED CT | Systematic Assessment |
|
| Thrombocytopenia | Investigations | SNOMED CT | Systematic Assessment |
|
| Ventricular tachycardia | Cardiac disorders | SNOMED CT | Systematic Assessment |
|
Not provided
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| D008173 |
| Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
|
| SF-36 norm-based general health score |
|
| SF-36 norm-based vitality score |
|
| SF-36 norm-based social functioning score |
|
| SF-36 norm-based role-emotional score |
|
| SF-36 norm-based mental health score |
|
| SF-36 standardized physical component score |
|
| SF-36 standardized mental component score |
|
| .18 |
| Superiority |
| SF-36 norm-based bodily pain score | Wilcoxon (Mann-Whitney) | .48 | Superiority |
| SF-36 norm-based general health score | Wilcoxon (Mann-Whitney) | .26 | Superiority |
| SF-36 norm-based vitality score | Wilcoxon (Mann-Whitney) | .23 | Superiority |
| SF-36 norm-based social functioning score | Wilcoxon (Mann-Whitney) | .36 | Superiority |
| SF-36 norm-based role-emotional score | Wilcoxon (Mann-Whitney) | .41 | Superiority |
| SF-36 norm-based mental health score | Wilcoxon (Mann-Whitney) | .80 | Superiority |
| SF-36 standardized physical component score | Wilcoxon (Mann-Whitney) | .80 | Superiority |
| SF-36 standardized mental component score | Wilcoxon (Mann-Whitney) | .23 | Superiority |
|
| FACT functional well-being |
|
| FACT BMT subscale |
|
| FACT trial outcome index |
|
| FACT-G |
|
| FACT-BMT total |
|
| 0.1 |
| Superiority |
| FACT emotional well-being | Wilcoxon (Mann-Whitney) | 0.63 | Superiority |
| FACT functional well-being | Wilcoxon (Mann-Whitney) | 0.78 | Superiority |
| FACT BMT subscale | Wilcoxon (Mann-Whitney) | .84 | Superiority |
| FACT trial outcome index | Wilcoxon (Mann-Whitney) | .37 | Superiority |
| FACT-G | Wilcoxon (Mann-Whitney) | .71 | Superiority |
| FACT-BMT total | Wilcoxon (Mann-Whitney) | .54 | Superiority |
| Title | Measurements |
|---|---|
|
| .39 |
| Superiority |
| Modified HAP adjusted activity score | Wilcoxon (Mann-Whitney) | .39 | Superiority |
| Title | Measurements |
|---|---|
|
| LSS eye scale |
|
| LSS nutrition scale |
|
| LSS psychological scale |
|
| LSS mouth scale |
|
| LSS overall summary scale |
|
| .007 |
| Superiority |
| Lee symptom lung scale | Wilcoxon (Mann-Whitney) | .20 | Superiority |
| Lee symptom eye scale | Wilcoxon (Mann-Whitney) | .002 | Superiority |
| Lee symptom nutrition scale | Wilcoxon (Mann-Whitney) | .52 | Superiority |
| Lee symptom psychological scale | Wilcoxon (Mann-Whitney) | .22 | Superiority |
| Lee symptom mouth scale | Wilcoxon (Mann-Whitney) | .002 | Superiority |
| Lee symptom overall summary scale | Wilcoxon (Mann-Whitney) | <0.001 | Superiority |