A Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD
Approximately 10,000 allogeneic hematopoietic stem cell transplants (HSCT) are performed annually in the US for various indications. Bronchiolitis obliterans (BO) is the most common late noninfectious complication following allogeneic hematopoietic stem cell transplant. Prognosis of BO in the allogeneic HSCT setting is dismal and there are no therapies proven to be consistently effective. The exact incidence is not clear but may be as high as 30%2 . Risk factors include new or ongoing chronic graft versus host disease (cGVHD), age, antecedent obstructive airways disease and viral infections1. BO is characterized physiologically by progressive irreversible airflow obstruction and pathologically by luminal occlusion of the distal airways due to progressive scarring3. The pathogenesis is not completely understood but the cytokine transforming growth factor-beta 1 (TGF-b1), important for both tissue repair and fibrosis, is thought to play a pivotal role. Bortezomib, an FDA approved proteasomal inhibitor inhibits TGF-b1 signaling in vitro and protects against lung injury/fibrosis in bleomycin mouse model as well as in a mouse model for skin fibrosis. This is consistent with other data in the literature that proteasomal inhibition can prevent the development of fibrosis. Thus the investigators propose to test the safety, tolerability and efficacy of bortezomib in chronic pulmonary GVHD (BO).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Proposal to Test the Efficacy and Tolerability of Bortezomib in Pulmonary Chronic GVHD|
- Change in pulmonary function as measured by FEV1 from baseline and 9 weeks later. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]Research subjects will receive 2 4 week cycles of bortezomib with a 1 week holiday between cycles.
- Exercise Tolerance- 6 minute walk at baseline and 9 weeks later. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
- Quality of Life-SF-36 at baseline and 9 weeks later. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Patients will Receive 2 4week cycles of Bortezomib. Each cycle will consist of weekly bortezomib with a 2 week interval between cycles.
Each patient will receive 2 cycles of Bortezomib. For each cycle Bortezomib wil be given once a week, 1.3mg/m2 for 4 weeks with 2 weeks between each cycle.
Other Name: Velcade
Please refer to this study by its ClinicalTrials.gov identifier: NCT01163786
|Contact: Manu Jain, MD||312-908-8163|
|Contact: Study Coordinatorfirstname.lastname@example.org|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Principal Investigator: Manu Jain, MD, MS|
|Principal Investigator: Jayesh Mehta, MD|
|Principal Investigator:||Manu Jain, MD, MS||Northwestern University|
|Principal Investigator:||Jayesh Mehta, MD||Northwestern University|