In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus

Phase 1

Terminated

• Conditions: Graft Versus Host Disease
• Interventions: Drug: Cyclophosphamide and Sirolimus; Drug: Low dose IL-2 with Cytoxan + Sirolimus; Drug: Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus; Drug: Low dose IL-2, Vidaza, Cytoxan & Sirolimus

• Registration Number: NCT01453140
• Lead Sponsor: Hackensack Meridian Health

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.

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-10-13
• Study First Submitted QC: 2011-10-14
• Study First Posted: 2011-10-17
• Primary Completion: 2012-03
• Study Completion: 2012-07
• Results First Submitted: 2013-07-30
• Status Verified: 2022-02
• Results First Submitted QC: 2022-02-04
• Last Update Submitted: 2022-02-04
• Results First Posted: 2022-03-02
• Last Update Posted: 2022-03-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclophosphamide and Sirolimus	Cyclophosphamide and Sirolimus	cyclophosphamide and sirolimus combo
Lowdose IL-2, Cytoxan + Sirolimus	Low dose IL-2 with Cytoxan + Sirolimus	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.
Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus	Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus	Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) \& Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).
Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus	Low dose IL-2, Vidaza, Cytoxan & Sirolimus	Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) \& Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).

Primary Outcome Measures

Name	Time	Method
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.	28 days to 100 days post transplant	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.

Trial Locations

Locations (1)

John Theurer Cancer Center at Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States