In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus (T-REG)

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

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

Study Overview

• Status: Terminated
• Conditions: Graft Versus Host Disease
• Intervention / Treatment: Drug: Cyclophosphamide and Sirolimus; Drug: Cyclophosphamide and Sirolimus; Drug: Low dose IL-2 with Cytoxan + 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

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclophosphamide and Sirolimus; cyclophosphamide and sirolimus combo	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.; Other Names: Cytoxan; Drug: Cyclophosphamide and Sirolimus; Day 1: Cyclophosphamide Day 2: Sirolimus; Other Names: Other names: Cytoxan
Experimental: Lowdose IL-2, 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.	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.; Other Names: Cytoxan; Interleukin-2; 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; Other Names: Cytoxan; Interleukin-2; Other names:
Experimental: Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus; Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) & Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).	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.; Other Names: Cytoxan; Interleukin-2; Azactidine; Drug: Low dose IL-2, Vidaza, Cytoxan & Sirolimus; Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.; Other Names: Cytoxan; Interleukin-2; Other names:; Azactidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Hackensack Meridian Health
• Investigators: Principal Investigator: Michele Donato, MD, Hackensack Meridian Health

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimated): October 17, 2011

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Aza Compounds; Nucleosides; Ribonucleosides; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukins; Lymphokines; Sirolimus; Cyclophosphamide; Azacitidine; Interleukin-2
• Other Study ID Numbers: Pro00002219