In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus With or Without Vidaza (Azacitidine) for Steroid-refractory Acute Graft-versus-host Disease

• Status: Completed
• Trial end date: 2012-07-01
• Target enrollment: 0
• Participant gender: All

Summary

In this study the investigators are proposing to treat patients with steroid-refractory Graft-versus-host Disease (GVHD) in a manner designed to promote CD4+CD25+FoxP3+ Tregs. The profound immune suppression which follows the most common salvage treatment for GVHD have unfortunately lead to very poor outcomes because of high infection rates. A more targeted approach based on the promotion and stabilization of Tregs is hoped to allow GVHD control without the profound immunosuppression usually seen. High-dose cyclophosphamide and sirolimus have been successfully used for the prevention of 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hackensack Meridian Health; Hackensack University Medical Center
• Treatments: Azacitidine; Cyclophosphamide; Everolimus; Interleukin-2; Sirolimus

Criteria

Inclusion Criteria:

• Patients must have a documented clinical diagnosis of grade II-IV acute graft-versus- host disease defined as 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 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.