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

NCT05250037 | Recruiting

• 4 other identifiers: RG1121806NCI-2021-1337510767R01HL161037
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 4

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.

Conditions

Bronchiolitis Obliterans Syndrome; Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of bronchiolitis obliterans syndrome (BOS)

  Diagnosed by National Institute of Health criteria or clinical diagnosis in the absence of alternative diagnosis.

  Up to 2 years

• Pulmonary impairment

  Defined by temporal decline in forced expiratory volume in the first second (FEV1) determined by assessment of spirometry data.

  Up to 2 years

Secondary Outcomes (6)

• Time from respiratory viral infection and chronic graft-versus-host disease to FEV1 decline

  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

• Incidence of late onset noninfectious pulmonary complications

  Up to 2 years

• Incidence of non-viral infectious pulmonary complications

  Up to 2 years

Study Arms (1)

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.

Procedure: Home spirometry; Procedure: Biospecimen Collection; Other: Questionnaire Administration

Interventions

Home spirometry PROCEDURE

Undergo spirometry measurements

Also known as: SPIROMETRY

Screening (spirometry measurements)

Biospecimen Collection PROCEDURE

Undergo nasal and/or oral swabs, and blood collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Screening (spirometry measurements)

Questionnaire Administration OTHER

Complete questionnaires

Screening (spirometry measurements)

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Allogeneic hematopoietic cell transplant recipients, age 8 and up.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Stanford Cancer Institute

Palo Alto, California, 94304, United States

RECRUITING

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum, PBMC and nasal swabs.

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Hematologic Neoplasms

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Guang-Shing Cheng, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guang-Shing Cheng, MD

CONTACT

206.667.7074; gcheng2@fredhutch.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: February 22, 2022
• Study Start: March 30, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)