A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

Inclusion Criteria:

- Histologically-confirmed active chronic GVHD >100 days following
allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has
failed prior therapy. In the event that histological confirmation poses undue risk,
clinical evaluation is sufficient.

- Women must have a negative pregnancy test before sirolimus administration and women
of child-bearing potential agree to use a medically acceptable contraceptive
throughout the treatment period and for 3 months after discontinuation of sirolimus.
Any woman becoming pregnant during the treatment period must discontinue the use of
sirolimus.

- Absolute neutrophil count (ANC) >1000/mm^3, unless receiving G-CSF to maintain
neutrophil count >500/mm^3

- Discontinuation of cyclosporine or FK506 at the time of initiating sirolimus with
cyclosporine trough level <100 mg/dl and FK506 level < 5 mg/dl

- Karnofsky performance score > or = 50 during pre-study screening

- Written, signed, and dated informed consent

Exclusion Criteria:- Uncontrolled systemic infection

- Unstable disease states (i.e., hepatic failure, ventilatory-dependent respiratory
failure, etc.)

- Serum creatinine > or = 3.0 mg/dL, platelet count < or = 50,000/mm^3

- History of Post-transplant microangiopathic hemolytic anemia

- Uncontrolled hyperlipidemia

- Use of any investigational drug within 4 weeks of entry into the study

- Use of methotrexate or antibody therapies within 24 hours of sirolimus administration

- Inability to tolerate oral therapy for any reason

- Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study
screening

- Known hypersensitivity to macrolide antibiotics