Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

• Status: Completed
• Trial end date: 2012-08-01
• Target enrollment: 0
• Participant gender: All

Summary

To study the effectiveness of an immunosuppressive drug sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Treatments: Everolimus; Prednisone; Sirolimus

Criteria

Inclusion Criteria:

• Age ≥ 13 years

• Weight ≥ 40 kg.

• Biopsy or clinical presentation diagnostic of chronic GVHD >100 days following allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has failed prior corticosteroid therapy or corticosteroid taper. In the event that histological confirmation poses undue risk, clinical evaluation is sufficient.

• Women of child-bearing potential must have a negative pregnancy test before sirolimus administration and agree to use a medically acceptable contraceptive throughout the treatment period until 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/mm³, unless receiving G-CSF to maintain neutrophil count > 500/mm³.

• At the time of initiating sirolimus the cyclosporine trough level is recommended to be < 100 mg/dl and FK506 level is recommended to be < 5 mg/dl. FK506 or cyclosporine is to be discontinued soon after initiation of sirolimus.

• Karnofsky performance score ≥ 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 ≥ 3.0 mg/dL

• Platelet count ≤ 50,000/mm³

• 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