Study Stopped
Dose Limiting Toxicities
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
1 other identifier
interventional
3
1 country
1
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2011
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2011
CompletedFirst Submitted
Initial submission to the registry
October 13, 2011
CompletedFirst Posted
Study publicly available on registry
October 17, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2012
CompletedResults Posted
Study results publicly available
March 2, 2022
CompletedApril 8, 2026
March 1, 2026
7 months
October 13, 2011
July 30, 2013
March 20, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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
Study Arms (3)
Cyclophosphamide and Sirolimus
EXPERIMENTALcyclophosphamide and sirolimus combo
Lowdose IL-2, Cytoxan + Sirolimus
EXPERIMENTALLow 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
EXPERIMENTALLowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) \& Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).
Interventions
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.
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.
Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
3 patients enrolled - all 3 had grade 4 (possibly treatment related) limiting toxicities. All three patients have since passed away. Study was closed after being on hold as per stopping rules.
Results Point of Contact
- Title
- Dr. Michele Donato, MD
- Organization
- Hackensack University Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Michele Donato, MD
Hackensack Meridian Health
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 13, 2011
First Posted
October 17, 2011
Study Start
August 1, 2011
Primary Completion
March 1, 2012
Study Completion
July 1, 2012
Last Updated
April 8, 2026
Results First Posted
March 2, 2022
Record last verified: 2026-03