The Longitudinal Impact of Respiratory Viruses on Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation (The RV-BOS Study)
Overview
- Phase
- Not Applicable
- Intervention
- Home spirometry
- Conditions
- Bronchiolitis Obliterans Syndrome
- Sponsor
- Fred Hutchinson Cancer Center
- Enrollment
- 250
- Locations
- 8
- Primary Endpoint
- Pulmonary impairment
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This observational trial studies whether respiratory viruses are the cause of lung disease (bronchiolitis obliterans syndrome [BOS] or graft-versus-host disease of the lung) and changes in lung function in patients who have received a donor stem cell transplant. Patients with chronic graft-versus-host disease (cGVHD) are at higher risk of developing BOS. Studies have also shown that patients who had a respiratory viral illness early after their transplant are at higher risk of developing lung problems later on. Patients who are at risk and who already have BOS might benefit from being monitored more closely. Spirometry is a way of assessing a patient's lung function and is often used to diagnose lung disease. Spirometry measured at home with a simple handheld device may reduce the burden of performing pulmonary function testing at a facility and potentially help patients get their lung disease diagnosed and treated sooner.
Detailed Description
OUTLINE: This is an observational study. Patients undergo home spirometry measurements with a portable handheld spirometer and complete questionnaires weekly, a nasal swab for viral polymerase chain reaction (PCR) surveillance every 4 weeks, and undergo blood collection and nasal swabs every 3 months for up to 2 years. (The minimum required follow-up is 1 year, but there is an optional 1 year extension period.)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Allogeneic HCT recipients with any indication, graft source, donor type, or conditioning regimen
- •Age 8 and older
- •COHORT 1 Inclusion criteria: One or more of the following clinical scenarios that encompass increased risk for BOS:
- •A diagnosis of cGVHD as per NIH criteria through 5 years of diagnosis.
- •i. New diagnosis of cGVHD within 3 months. This window may be extended by 30 days on a case-by-case basis.
- •ii. A diagnosis of cGVHD ≥ 3 months ≤ 5 years with a new FEV1 decline of ≥10% in absolute compared with prior 2 years PFT.
- •iii. A recent documented respiratory infection of any etiology that has been clinically managed and stabilized or improving as determined by a clinician, within 8 weeks.
- •iv. Progression of flare of chronic GVHD requiring an alteration in therapy as determined by a clinician, within 3 months.
- •At 'Day 80' evaluation. D80 designates posttransplant landmark, usually between 70-120 days, in which patients are evaluated for discharge back to community care. Patients with the following occurrences can be enrolled with 3 months of the Day 80 post-transplant evaluation.
- •i. FEV1 decline of 10% in absolute values compared with pretransplant baseline. ii. Documented posttransplant RVI. iii. Lower respiratory tract disease (LRTD) of any etiology.
Exclusion Criteria
- •Life expectancy \< 2 years.
- •Diagnosis of active hematologic relapse or malignancy requiring active treatment that will affect that patient's ability to comply with study procedures.
- •Patient should not have a clinically acute active lower respiratory tract infection or a clinically acute active noninfectious respiratory condition (i.e. COPD exacerbation, pleural effusion) at the time of enrollment. However, patient may become eligible once these conditions have stabilized or resolved as noted above.
- •Inability or unwillingness to perform the study procedures, most of which are performed at home.
- •Lack of a personal iOS or Android smartphone.
- •Inability or unwillingness to communicate electronically.
Arms & Interventions
Screening (spirometry measurements)
Patients undergo home spirometry measurements with a portable handheld spirometer and complete questionnaires weekly, a nasal swab for viral polymerase chain reaction (PCR) surveillance every 4 weeks, and undergo blood collection and nasal swabs every 3 months for up to 2 years.
Intervention: Home spirometry
Screening (spirometry measurements)
Patients undergo home spirometry measurements with a portable handheld spirometer and complete questionnaires weekly, a nasal swab for viral polymerase chain reaction (PCR) surveillance every 4 weeks, and undergo blood collection and nasal swabs every 3 months for up to 2 years.
Intervention: Biospecimen Collection
Screening (spirometry measurements)
Patients undergo home spirometry measurements with a portable handheld spirometer and complete questionnaires weekly, a nasal swab for viral polymerase chain reaction (PCR) surveillance every 4 weeks, and undergo blood collection and nasal swabs every 3 months for up to 2 years.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Pulmonary impairment
Time Frame: Up to 2 years
Defined by temporal decline in forced expiratory volume in the first second (FEV1) determined by assessment of spirometry data.
Incidence of bronchiolitis obliterans syndrome (BOS)
Time Frame: Up to 2 years
Diagnosed by National Institute of Health criteria or clinical diagnosis in the absence of alternative diagnosis.
Secondary Outcomes
- Incidence of non-viral infectious pulmonary complications(Up to 2 years)
- FEV1 (percent predicted) at clinical recognition of BOS(Up to 2 years)
- Incidence of asymptomatic and symptomatic viral infections(Up to 2 years)
- Establishment of a biorepository that includes blood samples, respiratory viral samples, and nasal microbiome samples from patients with clinically recognized BOS(Up to 2 years)
- Incidence of late onset noninfectious pulmonary complications(Up to 2 years)
- Time from respiratory viral infection and chronic graft-versus-host disease to FEV1 decline(Up to 2 years)