Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

Phase 2

Recruiting

• Conditions: Hematologic Malignancy; Bronchiolitis Obliterans Syndrome
• Interventions: Drug: Ruxolitinib

• Registration Number: NCT05413356
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2022-05
• Study Start: 2022-06-01
• Study First Submitted: 2022-06-07
• Study First Submitted QC: 2022-06-07
• Study First Posted: 2022-06-10
• Last Update Submitted: 2022-10-18
• Last Update Posted: 2022-10-19
• Primary Completion: 2024-06-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
absolute FEV1 increase	3 Months	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)

Secondary Outcome Measures

Name	Time	Method
treatment failure rate	3 Months	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)
absolute FEV1 increase	6 Months, 9 Months, 12 Months and 24 Months	The proportion of participants with a sustained, absolute FEV1 increase by ≥ 10% after treatment with ruxolitinib (compared to baseline measure prior to study enrollment)
Improvements in chronic GVHD organ specific manifestations	6 Months, 9 Months, 12 Months and 24 Months	mprovements in chronic GVHD organ specific manifestations will be categorized according to the NIH chronic GVHD consensus criteria.
Overall Survival	2 years	The proportion of patients survival at two years after enrollment of ruxolitinib treatment
cGVHD progression-free survival	2 years	Participants alive without cGVHD progression are censored at the date of last disease evaluation
The incidence and types of serious adverse events	From the start of treatment until 30 days after the end of treatment, up to 2 years	Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE v4)
The change of systemic corticosteroid dose over time	From the start of treatment until the end of treatment, up to 2 years	The change of systemic corticosteroid dose over time during the treatment of BOS

Trial Locations

Locations (1)

The first Affiliated Hospital of Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China