Clinical trial NCT05413356: Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome
Official title: Ruxolitinib for Newly Diagnosed Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Bronchiolitis Obliterans Syndrome
Hematologic Malignancy
Keywords: Allogeneic Hematopoietic stem cell transplantation
chronic graft versus host disease
bronchiolitis obliterans syndrome
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Zhejiang Provincial People's Hospital
name: The First Affiliated Hospital of Zhejiang Chinese Medical University
name: Sir Run Run Shaw Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: Ningbo No. 1 Hospital
name: The Affiliated People's Hospital of Ningbo University
name: Jinhua Central Hospital
name: Taizhou Hospital
name: Union hospital of Fujian Medical University
name: Xiangya Hospital of Central South University
First posted: 2022-06-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: absolute FEV1 increase
timeFrame: 3 Months
Secondary outcomes:
measure: treatment failure rate
timeFrame: 3 Months
measure: absolute FEV1 increase
timeFrame: 6 Months, 9 Months, 12 Months and 24 Months
measure: Improvements in chronic GVHD organ specific manifestations
timeFrame: 6 Months, 9 Months, 12 Months and 24 Months
measure: Overall Survival
timeFrame: 2 years
measure: cGVHD progression-free survival
timeFrame: 2 years
measure: The incidence and types of serious adverse events
timeFrame: From the start of treatment until 30 days after the end of treatment, up to 2 years
measure: The change of systemic corticosteroid dose over time
timeFrame: From the start of treatment until the end of treatment, up to 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: First Affilaated Hospital of Medical School of Zhejiang University
name: Yi Luo, M.D.
role: PRINCIPAL_INVESTIGATOR
References: