Clinical trial NCT01327625: Efficacy Study of Azithromycin-based Therapy for Bronchiolitis Obliterans
Official title: A Pilot Study Evaluating the Efficacy of Azithromycin, N-acetylcystein and Inhaled Corticosteroid Combination Therapy for Bronchiolitis Obliterans After Allogeneic Hematopoietic Cell Transpantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Graft vs Host Disease
Bronchiolitis Obliterans
Keywords: Allogeneic hematopoietic cell transplantation
Graft versus host disease
Bronchiolitis obliterans
Azithromycin
N-acetylcystein
Fluticasone
Inhaled steroid
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2011-04-01
Enrollment: 6
Sex: ALL
Minimum age (years): 15
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Response rate based on the improvement of FEV1
timeFrame: 6 months
Secondary outcomes:
measure: Clinical benefit rate based on the degree of change in FEV1
timeFrame: 6 months
measure: change in FEV1 compared with pretreatment level
timeFrame: 6 months after treatment initiation
measure: Reduction rate in immunosuppressive agent / systemic corticosteroid
timeFrame: 6 months after treatment initiation
measure: Discontinuation rate in immunosuppressive agent / systemic corticosteroid
timeFrame: 6 months after treatment initiation
measure: Change in dose-intensity of immunosuppressive agent / systemic corticosteroid compared with pretreatment dose-intensity
timeFrame: 6 months after treatment initiation
measure: event-free survival
timeFrame: 1 year
measure: overall survival
timeFrame: 1year
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Dae-Young Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
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