The Longitudinal Impact of Respiratory Viruses on Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation (The RV-BOS Study)

NCT ID: NCT05250037

Last Updated: 2026-01-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 250 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-03-30
• Study Completion Date: 2028-06-30

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.)

Conditions

Bronchiolitis Obliterans Syndrome; Hematopoietic and Lymphoid Cell Neoplasm

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Home spirometry

Intervention Type: PROCEDURE

Undergo spirometry measurements

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo nasal and/or oral swabs, and blood collection

Questionnaire Administration

Intervention Type: OTHER

Complete questionnaires

Interventions

Home spirometry

Undergo spirometry measurements

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo nasal and/or oral swabs, and blood collection

Intervention Type: PROCEDURE

Questionnaire Administration

Complete questionnaires

Intervention Type: OTHER

Other Intervention Names

SPIROMETRY; Biological Sample Collection; Biospecimen Collected; Specimen Collection

Eligibility Criteria

Inclusion Criteria

• Allogeneic HCT recipients with any indication, graft source, donor type, or conditioning regimen
• Age 8 and older

1. 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.

2. 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.

1. "Early BOS", ie patients with new airflow decline and obstruction, not yet meeting the FEV1 cut-off of < 75% predicted by FEV1, in the absence of other etiologies as determined by clinical investigations including chest imaging and microbiologic studies.

2. NIH-defined BOS:

i. FEV1 < 75% predicted, with a decline in absolute FEV1 > 10% compared to pretransplant baseline or within the prior 2 years. Absolute decline in FEV1 should remain >10% after bronchodilator response.

ii. FEV1/FVC or FEV1/VC <0.7, or Lower Limit of Normal as per accepted reference standards. Reference standards may include National Health and Nutrition Examination Survey III or Global Lung Initiative.

iii. Absence of an alternative diagnosis, including COPD exacerbation, asthma, and active respiratory tract infection, as determined by appropriate clinical investigations that may include chest imaging, microbiologic cultures, and/or bronchoscopy.

iv. One of two supportive features of BOS:

• a. Evidence of air trapping by PFTs: RV>120%, or elevated RV/TLC (>20% of predicted value)
• b. High resolution chest CT with inspiratory and expiratory cuts that show findings that are consistent with small airways disease including (but not exclusive of) air trapping, bronchial wall thickening, or bronchiectasis.

3. BOS with atypical spirometric pattern

i. FEV1 <80%, with a preserved FEV1/FVC ratio (≥0.7) and TLC ≥80% in the absence of other clinically determined lung disease.

4. Clinical or suspected diagnosis of BOS not otherwise meeting above criteria.

• Patient should have an Android or iOS-based smartphone with reliable access to Wi-Fi for data to be transmitted electronically. Android smartphones should have a software version of 4.0 or higher; iOS phones should have a version of 8.0 or higher.
• Patient should be willing and able to communicate electronically in English or Spanish.

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.

• Minimum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guang-Shing Cheng, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Stanford Cancer Institute

Palo Alto, California, United States

Site Status: RECRUITING

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Site Status: RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Guang-Shing Cheng, MD

Role: CONTACT

gcheng2@fredhutch.org

206.667.7074

Facility Contacts

Joe Hsu, MD, MPH

Role: primary

joehsu@stanford.edu

650-724-7061

Maria Hollobaugh

Role: primary

mholloba@med.umich.edu

734-647-6714

Anum Waqar

Role: primary

awaqar@mdanderson.org

713-834-9677

Guang-Shing Cheng, MD

Role: primary

gcheng2@fredhutch.org

206-667-7074

Other Identifiers

NCI-2021-13375

Identifier Type: REGISTRY

Identifier Source: secondary_id

10767

Identifier Type: OTHER

Identifier Source: secondary_id

R01HL161037

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RG1121806

Identifier Type: -

Identifier Source: org_study_id