Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

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

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

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.

Allogeneic Hematopoietic stem cell transplantation, chronic graft versus host disease, bronchiolitis obliterans syndrome

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

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.

Inclusion Criteria: Male or female; 18-65 years old Diagnosis of BOS after allo-HCT defined as the 2014 NIH criteria Life expectancy > 6 months at the time of enrollment At least 4 weeks since initiation of the most recent systemic therapy for cGVHD or BOS The ability to understand and willingness to sign a written consent document Exclusion Criteria: Recurrent malignancy or disease progression requiring anticancer therapy Currently receiving or have previously received ruxolitinib for chronic GVHD therapy Known history of allergy to ruxolitinib or its excipients Hepatic dysfunction: transaminases (ALT, AST) > 5X ULN and/or total bilirubin > 3X ULN Hematologic dysfunction: absolute neutrophil count <1000/μL, platelet cout <30*10E9/L, and/or Hgb < 8 g/dL Renal dysfunction: calculated creatinine clearance < 30 mL/min (Cockcroft-Gault formula) previously received second-line treatment or any drugs in clinical trials for cGVHD