Impact of respiratory viruses on lung disease after stem cell transplant

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

This study is trying to see how respiratory viruses affect lung problems in people who have had a stem cell transplant, by monitoring their lung function and health over two years.

Quick facts

• Study type: Observational
• Enrollment: 250 (estimated)
• Ages: 8 Years and up
• Sex: All
• Sponsor: Fred Hutchinson Cancer Center (Academic / other)
• Locations: 4 sites (Palo Alto, California and 3 other locations)
• Trial ID: NCT05250037 on ClinicalTrials.gov

What this trial studies

This observational study investigates the relationship between respiratory viruses and the development of bronchiolitis obliterans syndrome (BOS) in patients who have undergone allogeneic hematopoietic cell transplantation. Participants will use a portable spirometer at home to monitor lung function and complete weekly questionnaires, while also undergoing viral surveillance through nasal swabs every four weeks and blood collection every three months for up to two years. The goal is to identify patients at higher risk for BOS and improve early diagnosis and treatment of lung complications.

Who should consider this trial

Good fit: Ideal candidates include allogeneic HCT recipients aged 8 and older, particularly those with chronic graft-versus-host disease or recent respiratory infections.

Not a fit: Patients who have not undergone allogeneic HCT or those without risk factors for BOS may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier diagnosis and better management of lung disease in patients post-transplant.

How similar studies have performed: Other studies have indicated a correlation between respiratory viral infections and lung complications in transplant patients, suggesting this approach may yield valuable insights.

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:

  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 and ≤ 5 years, with a new FEV1 decline of ≥10% in absolute value within 6 weeks compared with PFT done within the prior 2 years.

     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 a 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.
* COHORT 2 inclusion criteria: Newly diagnosed BOS within 6 weeks of clinical recognition. This may include the following scenarios:

  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:

* Diagnosis of BOS at time of enrollment (Cohort 1 only)
* 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.

Where this trial is running

Palo Alto, California and 3 other locations

• Stanford Cancer Institute — Palo Alto, California, United States (Recruiting)
• University of Michigan Cancer Center — Ann Arbor, Michigan, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Guang-Shing Cheng, MD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Guang-Shing Cheng, MD

Conditions Bronchiolitis Obliterans Syndrome; Hematopoietic and Lymphoid Cell Neoplasm