NCT01453140

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Hackensack Meridian Health · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Graft Versus Host Disease

Interventions

Type	Name	Description
DRUG	Cyclophosphamide and Sirolimus	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.
DRUG	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. 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.
DRUG	Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus	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.
DRUG	Cyclophosphamide and Sirolimus	Day 1: Cyclophosphamide Day 2: Sirolimus
DRUG	Low dose IL-2 with Cytoxan + Sirolimus	treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus
DRUG	Low dose IL-2, Vidaza, Cytoxan & Sirolimus	Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

Timeline

• Start date: 2011-08-01
• Primary completion: 2012-03-01
• Completion: 2012-07-01
• First posted: 2011-10-17
• Last updated: 2026-04-08
• Results posted: 2022-03-02

Locations

1 site across 1 country: United States