Rapamycin for Prevention of Chronic Graft-Versus-Host Disease
The objective of this study is to evaluate feasibility, toxicity and efficacy of using Rapamycin to prevent chronic graft-versus-host-disease (GVHD) during and after the tacrolimus taper in recipients of allogeneic stem cell transplant.
Our hypothesis is that the T cells that can cause chronic GVHD are suppressed but not eliminated by calcineurin inhibitors. Therefore, when the calcineurin inhibitors are discontinued, the T cells may get activated and result in GVHD. Rapamycin on the other hand will allow anergy formation and thus when discontinued, T cells should not get activated. The schedule is designed to have therapeutic rapamycin levels as the tacrolimus is discontinued. Rapamycin will be continued as a single agent for additional 4 weeks and be tapered off in two weeks.
|Graft Versus Host Disease||Drug: Rapamycin Drug: Tacrolimus||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Rapamycin for Prevention of Chronic Graft-Versus-Host Disease|
- Improvement of the Rate of Graft Versus Host Disease (GVHD) From the Accepted Rate of 74%. [ Time Frame: up to 8 weeks ]Percentage of patients free from graft versus host disease
- Overall Survival [ Time Frame: up to 10 weeks ]achieved overall survival in regard to leukemia
- Disease Free Survival [ Time Frame: up to 10 weeks ]achieved disease free in regard to leukemia
|Study Start Date:||February 2008|
|Study Completion Date:||August 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Rapamycin will be initiated 24 weeks post SCT, while the patient is on Tacrolimus. The initial dose of rapamycin is 12 mg of loading dose, followed by 4 mg daily. The dose will be adjusted to keep trough level at 3-12 ng/dl. Rapamycin will be continued at the therapeutic dose for 4 additional weeks after Tacrolimus is stopped. Rapamycin will then be tapered off over 2 weeks. The patients will be on 50% of steady state dose for one week and 25% of the steady state dose for the last week.
Other Names:Drug: Tacrolimus
Tacrolimus target level is 5-10 ng/dl. Tacrolimus taper will start at 26 weeks post SCT. Tacrolimus will be tapered off over 4-8 weeks. The rate of taper will be 25% every to weeks for patients on 4 mg or more tacrolimus daily. For the patients on 3 mg or less of tacrolimus, the dose will be reduced 1 mg every two weeks, and the last dose will be 1 mg every other day for two weeks.
Other Name: Prograf
Please refer to this study by its ClinicalTrials.gov identifier: NCT00623012
|United States, Connecticut|
|Yale University School of Medicine|
|New Haven, Connecticut, United States, 06520|
|Principal Investigator:||Stuart Seropian, M.D.||Yale University|