Bronchiolitis Obliterans Syndrome, Hematologic Malignancy
Conditions
Keywords
Allogeneic Hematopoietic stem cell transplantation, chronic graft versus host disease, bronchiolitis obliterans syndrome
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.
Interventions
DRUGRuxolitinib
Oral ruxolitinib twice daily
Sponsors
Taizhou Hospital
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
Union hospital of Fujian Medical University
Xiangya Hospital of Central South University
First Affiliated Hospital of Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| 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 |
| cGVHD progression-free survival | 2 years | Participants alive without cGVHD progression are censored at the date of last disease evaluation |
Countries
China
Contacts
Primary ContactYi Luo, M.D.
Backup ContactYibo Wu, M.D.
Outcome results
None listed