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Bronchiolitis Obliterans Syndrome

Bronchiolitis Obliterans

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Bronchiolitis Obliterans Organizing Pneumonia

Ruxolitinib twice daily treatment, combined with steroids 1mg/kg/day for two weeks, and tampering 0.25 mg/kg/day every week

Ruxolitinib

Yi Luo, M.D.

Yibo Wu, M.D.

Lung is one of the target organs in chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.

The incidence of chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 30%-70%, Which extremely limited the quality of life and the survival of patients after allo-HSCT. Lung is one of the target organs in cGVHD after allo-HSCT. Bronchiolitis obliterans syndrome (BOS) after allo-HSCT was a clinical syndrome characterized by persistent airflow restriction which is the result of lung cGVHD. BOS is one of the main causes of late mortality after allo-HSCT, severely restricting the daily activities and respiratory function of patients. It limits the quality of life and increased the non-relapse mortality (NRM) after allo-HSCT. Currently, the first-line treatment for BOS is FAM ( oral fluticasone, azithromycin and montelukast). However, more than 50% of patients develop as steroids resistant (SR)-BOS, and SR-BOS has a poor prognosis and irreversible impaired lung function. Ruxolitinib is an effective drug in the treatment of SR-cGVHD. This is a phase Ⅱ prospective clinical study to explore the efficacy and safety of ruxolitinib as a first-line treatment for newly diagnosed BOS after allo-HSCT.

Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment)

The proportion of participants who do not experience a sustained, absolute decrease in FEV1 by ≥ 10% after 3 months of treatment with ruxolitinib (compared to baseline measure prior to study enrollment)

The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after treatment with ruxolitinib (compared to baseline measure prior to study enrollment)

mprovements in chronic GVHD organ specific manifestations will be categorized according to the NIH chronic GVHD consensus criteria.

The proportion of patients survival at two years after enrollment of ruxolitinib treatment

Participants alive without cGVHD progression are censored at the date of last disease evaluation

Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE v4)

The change of systemic corticosteroid dose over time during the treatment of BOS

Second Affiliated Hospital, School of Medicine, Zhejiang University

Zhejiang Provincial People's Hospital

The First Affiliated Hospital of Zhejiang Chinese Medical University

Sir Run Run Shaw Hospital

First Affiliated Hospital of Wenzhou Medical University

Ningbo No. 1 Hospital

The Affiliated People's Hospital of Ningbo University

Jinhua Central Hospital

Taizhou Hospital

Union hospital of Fujian Medical University

Xiangya Hospital of Central South University

First Affiliated Hospital of Zhejiang University

Virus Diseases

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

Undergo nasal and/or oral swabs, and blood collection

Biospecimen Collection

Questionnaire Administration

Guang-Shing Cheng, MD

Joe Hsu, MD, MPH

Husham Sharifi, MD

Connie Varner

Greg Yanik, MD

Luis Vaquero

Ajay Sheshadri, MD

Amin Alousi, MD

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.

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.

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

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

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

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

Will be determined by the longitudinal follow-up of this observational study.

Will be determined by the longitudinal follow-up of this observational study. Follow-up of clinical encounters will provide an epidemiology of the incidence of noninfectious and infectious pulmonary complications.

The biorepository including self-collected samples will be catalogued and organized in a central location that can be easily accessed through a gatekeeper system.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome	NCT05413356	Bronchiolitis O... Hematologic Mal...	Ruxolitinib	18 Years - 65 Years	First Affiliated Hospital of Zhejiang University
The Longitudinal Impact of Respiratory Viruses on Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation (The RV-BOS Study)	NCT05250037	Bronchiolitis O... Hematopoietic a...	Home spirometry Biospecimen Col... Questionnaire A...	8 Years -	Fred Hutchinson Cancer Center
The Longitudinal Impact of Respiratory Viruses on Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Cell Transplantation (The RV-BOS Study)	NCT05250037	Bronchiolitis O... Hematopoietic a...	Home spirometry Biospecimen Col... Questionnaire A...	8 Years -	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for bronchiolitis obliterans syndrome