In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus

Phase I- II Study of in Vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus With or Without Vidaza (Azacitidine) for the Treatment of Steroid-refractory Acute Graft-versus-host Disease

In this study the investigators are proposing to treat patients with steroid-refractory Graft-versus-host Disease (GVHD) stabilization using IL-2 and azacitidine

High-dose cyclophosphamide and sirolimus have been successfully used for the prevention of Graft-versus-host Disease (GVHD) and have shown to enhance the Tregs subpopulation. The addition of low dose IL-2 and a demethylating agent such as azacitidine will also be studied in an attempt to promote and stabilize the FoxP3 expression of Tregs.

Inclusion Criteria:

• Patients must have a documented clinical diagnosis of grade II-IV acute graft-versus- host disease defined as graft versus host disease (GVHD) occurring within the first 100 days of transplantation
• Patients must be steroid-refractory defines as progression after 3 days of corticosteroid therapy or no response after 5 days of corticosteroid therapy.
• Progression is defined as up-grading
• No response is defined as no down-grading
• Progression after 3 days requires patients to have received at least 2 mg/mg/day for a total of 6 mg/kg of methylprednisolone or its equivalent.
• No response after 5 days requires patient to have received at least 2 mg/kg/d for a total of 10 mg/kg of methylprednisolone or its equivalent.
• Patients with exacerbation of GVHD during steroid taper will require re-treatment with 2mg/kg/d of corticosteroids and will need to meet the criteria
• Age 18-70
• Patients must have received an allogeneic hematopoietic stem cell transplant within 100 days of study enrollment.
• Serum creatinine < 2 mg/dL

Exclusion Criteria:

• Patients cannot have active central nervous system (CNS) disease.
• Patients must not have received cyclophosphamide for GVHD prophylaxis
• Patients must not have pneumonia requiring oxygen supplementation
• Unable or unwilling to sign informed consent.