Clinical Trial Detail

This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone, sirolimus/extracorporeal photopheresis plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to one of the two pre-specified experimental arms (Sirolimus + prednisone, Sirolimus + ECP + prednisone) or the comparator arm (Sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio.

- Suitable candidates are patients with chronic GVHD that is: a)High-risk (Platelets less than 100,000, greater than 50% skin involvement, bronchiolitis obliterans, or already being treated with prednisone greater than 0.5 mg/kg/day for a history of acute GVHD), newly diagnosed or not responding after up to 12 weeks of therapy with prednisone ± CNI ± an additional agent; b)Standard-risk and deemed inadequately responding after up to 12 weeks of therapy that began with prednisone at 0.5-1 mg/kg/day ± CNI; c) Inadequately responding to therapy with prednisone or sirolimus alone, or prednisone and ECP alone.

- Classic chronic GVHD with or without overlap syndrome but not late persistent or recurrent acute GVHD alone, diagnosed according to the NIH Consensus Working Group Guidelines and which requires treatment with systemic immunosuppressive medication.

- Weight more than or equal to 25 kg

- Patient or guardian willing and able to provide informed consent.

- Stated willingness to use contraception in women of childbearing potential.

- Stated willingness of patient to comply with study procedures and reporting requirements.

Other eligibility criteria may apply.

- Already receiving therapy with prednisone, sirolimus and CNI.

- Invasive fungal or viral infection not responding to appropriate antifungal or antiviral therapies.

- Inadequate renal function defined as measured creatinine clearance less than 50 mL/min/1.73 m^2 based on the Cockcroft-Gault formula (adults) or Schwartz formula (age < 12 years). Adults: eCCr (mL/min/1.73 m^2) = (140 - age) x mass (kg) x (0.85 if female)/72 x serum creatinine (mg/dL; Children: eCCr (mL/min/1.73 m^2) = k x height (cm) / serum creatinine (mg/dL) k = 0.33 (pre-term), 0.45 (full term to 1 year old), 0.55 (age 1-12 years).

- Inability to tolerate oral medications.

- Absolute neutrophil count < 1500 per microliter.

- Requirement for platelet transfusions other than to perform extracorporeal photopheresis.

- Pregnancy.

- Progressive or recurrent malignancy defined other than by quantitative molecular assays.

- Known hypersensitivity to sirolimus.

Other exclusion criteria may apply.