Cyclosporine Inhalation Solution (CIS) in Lung Transplant and Hematopoietic Stem Cell Transplant Recipients for the Treatment of Bronchiolitis Obliterans Syndrome

Summary

Background:

\- Bronchiolitis obliterans or bronchiolitis obliterans syndrome is a lung disorder that occurs as a complication of either lung transplantation or bone marrow/blood stem cell transplantation. One of the complications of transplant is the occurrence of graft versus host disease (in hematopoietic stem cell transplants) and host versus graft disease (in lung transplantation). In these diseases, the cells attack the lungs and cause irreversible small airway fibrosis referred to as bronchiolitis obliterans syndrome. When a patient develops fibrosis of the lungs or bronchioles, the lungs no longer work properly, which causes difficulties with breathing that lead to a diminished quality of life and an increased risk of death. Treatment typically involves immunosuppressive therapy such as oral cyclosporine or steroid therapy, but these treatments are only marginally effective and can cause significant toxicities and increase the risk of infections. Inhaled cyclosporine (CIS) achieves higher concentrations of cyclosporine in the lungs and lower concentrations of cyclosporine in the blood than oral cyclosporine. Therefore, it could have advantages over conventional oral immunosuppressive therapies used to treat this disorder. Researchers are interested in testing whether inhaled cyclosporine therapy could be used as a safe and effective treatment for bronchiolitis obliterans or bronchiolitis obliterans syndrome occurring after bone marrow/blood stem cell or lung transplants.

Objectives:

\- To evaluate whether inhaled cyclosporine (CIS) can improve or stabilize lung function and quality of life in individuals with bronchiolitis obliterans.

Eligibility:

\- Individuals between 10 and 80 years of age who have been diagnosed with bronchiolitis obliterans or bronchiolitis obliterans syndrome after blood or lung transplants.

Design:

* Participants will be screened with a full medical history and physical examination, as well as blood and urine tests, lung function tests, imaging studies, bronchoalveolar lavage samples, and quality of life questionnaires.
* Participants will take cyclosporine inhalation solution through a nebulizer. The nebulizer generates a mist of cyclosporine inhalation solution (CIS), which is then breathed in through a mouthpiece. The process takes approximately 20 minutes. The solution will be provided in single-use vials.
* Participants will continue to take all medications for post-transplant care as required by their doctor and the study researchers. Attempts will be made to reduce the doses and types of immunosuppressants given to participants on the study, as long as the treatment continues to produce improved or stable lung function.
* Participants will have study visits every 3 weeks with blood and urine tests, lung function tests, and imaging studies. Participants will undergo repeat bronchoalveolar sample at week 9 and 18. Participants will also complete quality of life questionnaires as directed. Treatment will continue for a minimum of 18 weeks, followed by a final follow-up visit 2 weeks after the end of the study.
* Participants who benefit from the inhaled cyclosporine (CIS) may continue to receive further therapy with inhaled cyclosporine at the end of the study by participation in a separate study extension.

Conditions

• Constrictive Bronchiolitis
• Bronchiolitis Obliterans
• Graft vs Host Disease
• Bronchiolitis, Exudative
• Bronchiolitis, Proliferative

Interventions

DRUG

Cyclosporine Inhalation Solution

sterile, clear, colorless, preservative-free solution of cyclosporine (USP) in propylene glycol developed specifically for administration by oral inhalation.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  lead NIH

Principal Investigators

• Nicole J Gormley, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

10 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-01-29

Primary Completion

2018-08-08

Completion

2018-08-08

FDA Drug

Yes

Countries

• United States

Study Locations