Efficacy Study of Azithromycin-based Therapy for Bronchiolitis Obliterans

Asan Medical Center6 enrolled

Overview

\[Study Objectives\] * 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.

* 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Graft vs Host Disease Bronchiolitis Obliterans

Interventions

azithromycin + N-acetylcystein + inhaled corticosteroidDRUG

* 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

Eligibility

Sex: ALLMin age: 15 YearsMax age: 75 Years

Medical Language ↔ Plain English

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)

Locations (1)

Asan Medical Center

Seoul, South Korea

Outcomes

Primary Outcomes

Response rate based on the improvement of FEV1

Response rate at 6 months after treatment initiation based on the improvement of FEV1

Time frame: 6 months

Secondary Outcomes

Clinical benefit rate based on the degree of change in FEV1

Clinical benefit rate at 6 months after treatment initiation based on the degree of change in FEV1

Time frame: 6 months

change in FEV1 compared with pretreatment level

Change in FEV1 at 6 months after treatment initiation compared with pretreatment level

Time frame: 6 months after treatment initiation

Reduction rate in immunosuppressive agent / systemic corticosteroid

Reduction rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation

Time frame: 6 months after treatment initiation

Discontinuation rate in immunosuppressive agent / systemic corticosteroid

Discontinuation rate in immunosuppressive agent / systemic corticosteroid at 6 months after treatment initiation

Time frame: 6 months after treatment initiation

Change in dose-intensity of immunosuppressive agent / systemic corticosteroid compared with pretreatment dose-intensity

Change in dose-intensity of immunosuppressive agent / systemic corticosteroid at 6 month after treatment initiation compared with pretreatment dose-intensity

Time frame: 6 months after treatment initiation

event-free survival

Time frame: 1 year

Data from ClinicalTrials.gov

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