In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus

Graft Versus Host Disease Clinical Trial

— T-REG  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01453140
• Other study ID #: TREG - Pro2219
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 2011
• Est. completion date: July 2012

Study information

• Verified date: February 2022
• Source: Hackensack Meridian Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

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

Locations

Country	Name	City	State
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Hackensack Meridian Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate of Patients With Steroid-refractory Graft-versus-host Disease (GVHD) Using Cyclophospahmide and Sirolimus Combined With 3 Variations of Low-dose IL 2 and Low-dose Vidaza.	The primary objective of this study is to determine the response rate of patients treated steroid-refractory graft-versus-host disease (GVHD) using cyclophospahmide and sirolimus combined with 3 variations of low-dose IL 2 and low-dose Vidaza with an outcome goal of promoting CD4+CD25+FoxP3+ Tregs.	28 days to 100 days post transplant