Conditions: Graft Versus Host Disease
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 3
Healthy volunteers: no

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

Detailed description:
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.

Arms:
arm 1: cyclophosphamide and sirolimus combo arm 2: Low dose IL-2 with Cytoxan + Sirolimus Patients in treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus. arm 3: Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) \& Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).

Interventions: intervention 1: Cyclophosphamide and Sirolimus intervention 2: Low dose IL-2 with Cytoxan + Sirolimus intervention 3: Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus intervention 4: Cyclophosphamide and Sirolimus intervention 5: Low dose IL-2 with Cytoxan + Sirolimus intervention 6: Low dose IL-2, Vidaza, Cytoxan & Sirolimus
Intervention descriptions: intervention 1: On the first day of treatment, cyclophosphamide will be administered at a dose of 4g/m2 IV x 1 dose. Patients who are \>40% above ideal weight will be dosed based on adjusted weight and adjusted BSA.

One day after the administration of cyclophosphamide, patients will receive sirolimus 6 mg PO x 1 and on the following day will start sirolimus at a dose of 2 mg PO daily. intervention 2: Patients in treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus.

IL-2 will be administered at a dose of 0.5E6 IU/m2 SQ daily x 8 weeks followed by 4 weeks off, starting 14 days after the cyclophosphamide. intervention 3: Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza). The Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

The dose administered will be 10 mg SQ daily for 5 days followed by 3 weeks off. intervention 4: Day 1: Cyclophosphamide Day 2: Sirolimus intervention 5: treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus intervention 6: Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

Protocol document: