This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone, sirolimus/extracorporeal photopheresis plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to one of the two pre-specified experimental arms (Sirolimus + prednisone, Sirolimus + ECP + prednisone) or the comparator arm (Sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio.
Background: Chronic GVHD is a medical condition that can become very serious. Chronic GVHD is a common development after allogeneic transplant that occurs when the donor cells attack and damage tissues. The primary purpose of this study is to compare treatment regimens that contain sirolimus without a calcineurin inhibitor to a comparator regimen of sirolimus with a calcineurin inhibitor and evaluate how well chronic GVHD responds to treatment. The combinations of medications in this study are:
- Sirolimus + calcineurin inhibitor + prednisone
- Sirolimus + extracorporeal photopheresis + prednisone
The goal is to select a treatment regimen for further comparison in the Phase III trial.
Design Narrative: The intent is to enroll subjects at the start of their initial therapy for high-risk chronic GVHD, or before their standard-risk chronic GVHD is refractory to glucocorticoid therapy, or is chronically dependent upon glucocorticoid therapy and multiple secondary systemic immunosuppressive agents. Patients will be stratified by transplant center and will be randomized to one of the three arms.
Only one of the two Phase II studies above will proceed into the Phase III component of the study.