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

February 4, 2022 updated by: Hackensack Meridian Health

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

Intervention / Treatment

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

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.
Time Frame: 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.
28 days to 100 days post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hackensack Meridian Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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 (ESTIMATE)

October 17, 2011

Study Record Updates

Last Update Posted (ACTUAL)

March 2, 2022

Last Update Submitted That Met QC Criteria

February 4, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TREG - Pro2219

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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