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

Primary Purpose

Graft Versus Host Disease

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide and Sirolimus
Low dose IL-2 with Cytoxan + Sirolimus
Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus
Cyclophosphamide and Sirolimus
Low dose IL-2 with Cytoxan + Sirolimus
Low dose IL-2, Vidaza, Cytoxan & Sirolimus
Sponsored by
Hackensack Meridian Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • John Theurer Cancer Center at Hackensack University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cyclophosphamide and Sirolimus

Lowdose IL-2, Cytoxan + Sirolimus

Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus

Arm Description

cyclophosphamide and sirolimus combo

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 (Cytoxan) & Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
October 13, 2011
Last Updated
February 4, 2022
Sponsor
Hackensack Meridian Health
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1. Study Identification

Unique Protocol Identification Number
NCT01453140
Brief Title
In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
Dose Limiting Toxicities
Study Start Date
August 2011 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hackensack Meridian Health

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cyclophosphamide and Sirolimus
Arm Type
Experimental
Arm Description
cyclophosphamide and sirolimus combo
Arm Title
Lowdose IL-2, Cytoxan + Sirolimus
Arm Type
Experimental
Arm Description
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.
Arm Title
Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus
Arm Type
Experimental
Arm Description
Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) & Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide and Sirolimus
Other Intervention Name(s)
Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Low dose IL-2 with Cytoxan + Sirolimus
Other Intervention Name(s)
Interleukin-2, Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus
Other Intervention Name(s)
Interleukin-2, Azactidine, Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide and Sirolimus
Other Intervention Name(s)
Other names: Cytoxan
Intervention Description
Day 1: Cyclophosphamide Day 2: Sirolimus
Intervention Type
Drug
Intervention Name(s)
Low dose IL-2 with Cytoxan + Sirolimus
Other Intervention Name(s)
Other names:, Interleukin-2, Cytoxan
Intervention Description
treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus
Intervention Type
Drug
Intervention Name(s)
Low dose IL-2, Vidaza, Cytoxan & Sirolimus
Other Intervention Name(s)
Other names:, Interleukin-2, Azactidine, Cytoxan
Intervention Description
Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
28 days to 100 days post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Donato, MD
Organizational Affiliation
Hackensack Meridian Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States

12. IPD Sharing Statement

Learn more about this trial

In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus

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