Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome

Sponsor

First Affiliated Hospital of Zhejiang University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05413356

Collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University (Other), Zhejiang Provincial People's Hospital (Other), The First Affiliated Hospital of Zhejiang Chinese Medical University (Other), Sir Run Run Shaw Hospital (Other), First Affiliated Hospital of Wenzhou Medical University (Other), Ningbo First People's Hospital (Other), The Affiliated People's Hospital of Ningbo University (Other), Jinhua Central Hospital (Other), Taizhou Hospital (Other), Union hospital of Fujian Medical University (Other), Xiangya Hospital of Central South University (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bronchiolitis Obliterans Syndrome Hematologic Malignancy	Drug: Ruxolitinib	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment group Ruxolitinib twice daily treatment	Drug: Ruxolitinib Oral ruxolitinib twice daily Other Names: Ruxolitinib twice daily

Arm

Intervention/Treatment

Experimental: treatment group

Ruxolitinib twice daily treatment

Drug: Ruxolitinib

Oral ruxolitinib twice daily

Other Names:

Ruxolitinib twice daily

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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