Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

Zhejiang University

Status and phase: Enrolling; Phase 2

Conditions: Hematologic Malignancy; Bronchiolitis Obliterans Syndrome

Treatments: Drug: Ruxolitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT05413356

ZJU-HSCT-BOS

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female; 18-65 years old
2. Diagnosis of BOS after allo-HCT defined as the 2014 NIH criteria
3. Life expectancy > 6 months at the time of enrollment
4. At least 4 weeks since initiation of the most recent systemic therapy for cGVHD or BOS
5. The ability to understand and willingness to sign a written consent document

Exclusion criteria

1. Recurrent malignancy or disease progression requiring anticancer therapy
2. Currently receiving or have previously received ruxolitinib for chronic GVHD therapy
3. Known history of allergy to ruxolitinib or its excipients
4. Hepatic dysfunction: transaminases (ALT, AST) > 5X ULN and/or total bilirubin > 3X ULN
5. Hematologic dysfunction: absolute neutrophil count <1000/μL, platelet cout <30*10E9/L, and/or Hgb < 8 g/dL
6. Renal dysfunction: calculated creatinine clearance < 30 mL/min (Cockcroft-Gault formula)
7. previously received second-line treatment or any drugs in clinical trials for cGVHD

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

treatment group

Experimental group

Description:

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

Treatment:

Drug: Ruxolitinib