A Pilot Study Evaluating the Efficacy of Azithromycin, N-acetylcystein and Inhaled Corticosteroid Combination Therapy for Bronchiolitis Obliterans After Allogeneic Hematopoietic Cell Transpantation
Overview
- Phase
- Not Applicable
- Intervention
- azithromycin + N-acetylcystein + inhaled corticosteroid
- Conditions
- Graft vs Host Disease
- Sponsor
- Asan Medical Center
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Response rate based on the improvement of FEV1
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
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.
Investigators
Dae-Young Kim
Assistant Professor
Asan Medical Center
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)
Arms & Interventions
Azithromycin
Patient who are diagnosed as bronchiolitis obliterans according to the WHO criteria
Intervention: azithromycin + N-acetylcystein + inhaled corticosteroid
Outcomes
Primary Outcomes
Response rate based on the improvement of FEV1
Time Frame: 6 months
Response rate at 6 months after treatment initiation based on the improvement of FEV1
Secondary Outcomes
- Clinical benefit rate based on the degree of change in FEV1(6 months)
- change in FEV1 compared with pretreatment level(6 months after treatment initiation)
- Reduction rate in immunosuppressive agent / systemic corticosteroid(6 months after treatment initiation)
- Discontinuation rate in immunosuppressive agent / systemic corticosteroid(6 months after treatment initiation)
- Change in dose-intensity of immunosuppressive agent / systemic corticosteroid compared with pretreatment dose-intensity(6 months after treatment initiation)
- event-free survival(1 year)
- overall survival(1year)