Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment

Inclusion Criteria:

• Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of

  • Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
  • Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
  • Absence of improvement after 3 months of primary treatment, or
  • Continued need for treatment with prednisone at doses >= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen
• Patient or guardian able and willing to provide informed consent
• Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)
• Stated willingness of the patient to comply with study procedures and reporting requirements
• Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements

Exclusion Criteria:

• Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
• Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
• Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
• Inability to tolerate oral medications
• Absolute neutrophil count (ANC) < 1500/uL
• Platelet count < 50,000/uL
• Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
• Pregnancy
• Known history of hypersensitivity to sirolimus