Trial Information

A PHASE I/II STUDY OF RAPAMYCIN (SIROLIMUS) IN COMBINATION WITH METHOTREXATE (MTX) AND CYCLOSPORINE (CPS) IN PATIENTS UNDERGOING MARROW TRANSPLANTATION FROM RELATED DONORS MISMATCHED FOR ONE HLA ANTIGEN IN THE DIRECTION OF GRAFT-VERSUS-HOST DISEASE (GVHD)

OBJECTIVES: I. Estimate the maximum tolerated dose of rapamycin that can be safely combined
with standard methotrexate/cyclosporine prophylaxis for graft-versus-host disease (GVHD) in
patients with hematologic disorders who have received a bone marrow transplant from a
related donor who is mismatched for 1 HLA-A, -B, or -DR antigen in the GVHD direction.

OUTLINE: This is a dose escalation study. Groups of 6-12 patients receive escalating doses
of rapamycin until the maximum tolerated dose of rapamycin given in combination with
methotrexate/cyclosporine is determined. All patients receive cyclosporine from the day
prior to transplant until day 50 post-transplant; the dose is then tapered over 130 days.
Methotrexate is given on days 1, 3, and 6 post-transplant. Rapamycin is given every other
day, days 7-59. Bone marrow transplantation occurs on day 0. Patients may not receive
concurrent therapy with agents that could interfere with rapamycin metabolism, intravenous
lipids, FK506 or other immunosuppressive agents (prednisone allowed), NSAIDs, or other
cytotoxic agents. Patients are followed at 6 months for 2 years, then annually.

PROJECTED ACCRUAL: 12-36 patients will be accrued over 1-2.5 years.