Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease
Condition: Graft vs Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Sirolimus; Prednisone
Intervention description: Patients will receive sirolimus at 2 mg/day orally with monitoring of trough drug levels weekly for 2 weeks to achieve trough drug levels 7-12 ng/ml. Along with prednisone therapy.; Prednisone therapy will remain at the dose the patient received at the time sirolimus was begun. Withdrawal of prednisone will began after first evidence of improvement of chronic GVHD.
Intervention MeSH terms: Sirolimus; Prednisone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No
Keywords: GVHD

Summary:

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

Eligibility 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