Bronchiolitis Obliterans, Graft vs Host Disease
Conditions
Keywords
Allogeneic hematopoietic cell transplantation, Graft versus host disease, Bronchiolitis obliterans, Azithromycin, N-acetylcystein, Fluticasone, Inhaled steroid
Brief summary
\[Study Objectives\] * To evaluate the efficacy of azithromycin, N-acetylcystein, and inhaled corticosteroid combination therapy in patients with bronchiolitis obliterans as a complication of allogeneic hematopoietic cell transplantation in terms of response rate at 6 months after treatment initiation based on the improvement of FEV1.
Detailed description
* Bronchiolitis obliterans (BO) is a graft-versus-host disease of respiratory organs. * Prognosis of BO is very poor, and the overall outcome of patients who are involved in BO is very dismal. * The mechanism of BO has been known to be associated with immune / non-immune response. * Corticosteroid and immunosuppressants are recommended as a best current treatment options for BO, which have been not satisfactory. * Many treatment options have been tried to improve the outcome of BO. * Azithromycin, as an immune modulating agent, has been tried for the treatment of BO, and has been reported to show hopeful results. * N-acetylcystein, as an antioxidative agent, has been tried for BO. * Inhaled corticosteroid may help to improve airway inflammation and decrease the amount of systemic corticosteroid. * These 3 drugs are widely used for other respiratory disease, have been proven to be safe, and have shown some efficacy for BO in various depth of evidence. * In these rationale, we'd like to try the 3-drug combination for BO, to assess the efficacy and safety of these drug combination.
Interventions
DRUGazithromycin + N-acetylcystein + inhaled corticosteroid
* Azithromycin 500mg qd x 1 week --\> 250mg qod x 6 months * N-acetylcystein 200mg tid x 6 months * Fluticasone 250mcg puff x2/day x 6 months
Sponsors
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients who previously received allogeneic hematopoietic cell transplantation due to hematologic malignancy, bone marrow failure syndrome, and other compatible disease. * Patients who are diagnosed as bronchiolitis obliterans (BO) according to the NIH diagnostic guideline which is suggested as below. * Patients should be 15 years of age or older, but younger than 75 years. * Patients should have estimated life expectancy of more than 3 months. * Patients must have adequate hepatic function (bilirubin less than 3.0 ㎎/㎗, AST and ALT less than three times the upper normal limit). * Patients must have adequate renal function (creatinine less than 2.0 ㎎/㎗).
Exclusion criteria
* Presence of significant active infection * Presence of uncontrolled bleeding * Any coexisting major illness or organ failure * Patients with a psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible. * Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception * Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate based on the improvement of FEV1 | 6 months | Response rate at 6 months after treatment initiation based on the improvement of FEV1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in FEV1 compared with pretreatment level | 6 months after treatment initiation | Change in FEV1 at 6 months after treatment initiation compared with pretreatment level |
| Reduction rate in immunosuppressive agent / systemic corticosteroid | 6 months after treatment initiation | Reduction rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation |
| Discontinuation rate in immunosuppressive agent / systemic corticosteroid | 6 months after treatment initiation | Discontinuation rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation |
| Clinical benefit rate based on the degree of change in FEV1 | 6 months | Clinical benefit rate at 6 months after treatment initiation based on the degree of change in FEV1 |
| event-free survival | 1 year | — |
| overall survival | 1year | — |
| Change in dose-intensity of immunosuppressive agent / systemic corticosteroid compared with pretreatment dose-intensity | 6 months after treatment initiation | Change in dose-intensity of immunosuppressive agent / systemic corticosteroid at 6 month after treatment initiation compared with pretreatment dose-intensity |
Countries
South Korea
Outcome results
None listed