Cyclosporine Inhalation Solution (CIS) in Lung Transplant and Hematopoietic Stem Cell Transplant Recipients for the Treatment of Bronchiolitis Obliterans Syndrome
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ClinicalTrials.gov Identifier: NCT01287078 |
Recruitment Status :
Completed
First Posted : February 1, 2011
Results First Posted : September 24, 2020
Last Update Posted : September 24, 2020
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Tracking Information | |||||
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First Submitted Date ICMJE | January 29, 2011 | ||||
First Posted Date ICMJE | February 1, 2011 | ||||
Results First Submitted Date ICMJE | August 3, 2020 | ||||
Results First Posted Date ICMJE | September 24, 2020 | ||||
Last Update Posted Date | September 24, 2020 | ||||
Study Start Date ICMJE | January 29, 2011 | ||||
Actual Primary Completion Date | August 8, 2018 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
The primary endpoint of each study group is FEV1 improvement or stabilization from study baseline by week 9 or thereafter, for at least two successive measures (efficacy) and the toxicity profile as measured by CTCAE criteria (safety)Asses... [ Time Frame: 4 years ] | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE | Not Provided | ||||
Original Secondary Outcome Measures ICMJE |
Secondary endpoints include PK and lung deposition characteristics improvement in chest CT images, results of cytokine arrays, and functional capacitythe study of pharmacokinetics and lung deposition characteristics of inhaled cyclosporine... [ Time Frame: 4 years ] | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Cyclosporine Inhalation Solution (CIS) in Lung Transplant and Hematopoietic Stem Cell Transplant Recipients for the Treatment of Bronchiolitis Obliterans Syndrome | ||||
Official Title ICMJE | Phase II Trial of Cyclosporine Inhalation Solution (CIS) in Lung Transplant and Hematopoietic Stem Cell Transplant Recipients for Treatment of Bronchiolitis Obliterans Syndrome | ||||
Brief 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:
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Detailed Description | Bronchiolitis Obliterans (BO) is an obstructive lung disease that can affect individuals that have undergone a lung or hematopoietic stem cell transplant. BO has been studied most extensively in lung transplant recipients, where it is considered to represent chronic lung rejection. It is the leading cause of death after lung transplant, with mortality rates up to 55%. In hematopoietic stem cell transplantation, BO is thought to be a manifestation of chronic graft-vs-host disease (GVHD). Up to 45% of patients undergoing hematopoietic stem cell transplantation at the NHLBI develop a decline in pulmonary function. Conventional therapy for patients who develop BO consists of augmentation of systemic immunosuppressants. Systemic immunosuppression has limited efficacy for BO and is associated with deleterious consequences including increased risk of infections and decreased graft-versus tumor/leukemia effects. Recently, cyclosporine inhalation solution (CIS) in solution with propylene glycol has been shown to improve overall survival and chronic rejection-free survival in lung transplant patients. These findings suggest targeted delivery of immunosuppressive therapy to the diseased organ warrants further investigation as this may minimize the morbidity associated with systemic immunosuppression. However, there currently exists limited data regarding the overall efficacy of inhaled cyclosporine to treat established BO following lung transplantation. Furthermore, inhaled cyclosporine has not been studied in the treatment of BO following hematopoietic stem cell transplantation. Here, we propose to evaluate the safety, efficacy, and pharmacodynamics of inhaled cyclosporine for the treatment of BO. Two distinct patient populations will be offered enrollment in this protocol: hematopoietic transplant recipients with BO (group A) and lung transplant recipients with BO (group B). Study participants will receive CIS at an initial dose of 150mg, three times weekly. Patients will undergo dose titration to a maximum dose of 300mg, three times weekly. Drug deposition and pharmacokinetic analyses will be performed at the initiation of treatment. Clinical parameters, including pulmonary function tests, will be measured in addition to laboratory markers of the anti-inflammatory response to CIS. Adverse events associated with treatment will be recorded. The primary objective is to 1) assess the safety and efficacy of inhaled cyclosporine as a new therapy in hematopoietic transplant patients and lung transplant patients with established BO. Additionally, we seek to promote a better understanding of the pathogenesis of BO in these two transplant groups and to assess the anti-inflammatory effects of inhaled cyclosporine in patients that develop this complication. The primary endpoint of each study group is the best response, FEV1 improvement or stabilization from study baseline at week 18 for two successive measures, at least 1 week apart, no more than 2 weeks apart. Secondary endpoints include the toxicity profile as measured by CTCAE criteria (safety), the study of pharmacokinetics and lung deposition characteristics of inhaled cyclosporine, improvement in high resolution chest CT images, results of peripheral blood and bronchoalveolar cytokine arrays to assess secondary markers of inflammation, and functional capacity measurements using a six-minute walk test. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: Cyclosporine Inhalation Solution
sterile, clear, colorless, preservative-free solution of cyclosporine (USP) in propylene glycol developed specifically for administration by oral inhalation.
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Study Arms ICMJE | Experimental: Inhaled Cyclosporine in Lung Transplant and HSCT Recipients
Subjects with Bronchiolitis Obliterans Syndrome (BOS) received cyclosporine inhalation solution (CIS) 150 mg, three times weekly during weeks 1-5. Dose escalated to 300 mg three times weekly from weeks 6-8. Study drug administration ended at week 19.
Intervention: Drug: Cyclosporine Inhalation Solution
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
25 | ||||
Original Estimated Enrollment ICMJE |
78 | ||||
Actual Study Completion Date ICMJE | August 8, 2018 | ||||
Actual Primary Completion Date | August 8, 2018 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
History of:<TAB> -Hematopoietic stem cell transplant recipients at least 99 days post transplant (group A) Or
And one of the following:
EXCLUSION CRITERIA:
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Sex/Gender ICMJE |
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Ages ICMJE | 10 Years to 80 Years (Child, Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT01287078 | ||||
Other Study ID Numbers ICMJE | 110068 11-H-0068 |
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Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ) | ||||
Original Responsible Party | Richard W. Childs, M.D./National Heart, Lung, and Blood Institute, National Institutes of Health | ||||
Current Study Sponsor ICMJE | National Heart, Lung, and Blood Institute (NHLBI) | ||||
Original Study Sponsor ICMJE | National Institutes of Health Clinical Center (CC) | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | ||||
Verification Date | August 31, 2018 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |