In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus With or Without Vidaza (Azacitidine) for Steroid-refractory Acute Graft-versus-host Disease
| Status: | Completed |
|---|---|
| Conditions: | Orthopedic, Hematology |
| Therapuetic Areas: | Hematology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 10/14/2017 |
| Start Date: | August 2011 |
| End Date: | July 2012 |
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) in a manner designed to promote CD4+CD25+FoxP3+ Tregs. The
profound immune suppression which follows the most common salvage treatment for GVHD have
unfortunately lead to very poor outcomes because of high infection rates. A more targeted
approach based on the promotion and stabilization of Tregs is hoped to allow GVHD control
without the profound immunosuppression usually seen. High-dose cyclophosphamide and sirolimus
have been successfully used for the prevention of 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.
Graft-versus-host Disease (GVHD) in a manner designed to promote CD4+CD25+FoxP3+ Tregs. The
profound immune suppression which follows the most common salvage treatment for GVHD have
unfortunately lead to very poor outcomes because of high infection rates. A more targeted
approach based on the promotion and stabilization of Tregs is hoped to allow GVHD control
without the profound immunosuppression usually seen. High-dose cyclophosphamide and sirolimus
have been successfully used for the prevention of 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.
Inclusion Criteria:
- Patients must have a documented clinical diagnosis of grade II-IV acute graft-versus-
host disease defined as 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 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.
We found this trial at
1
site
92 2nd St
Hackensack, New Jersey 07601
Hackensack, New Jersey 07601
(201) 996-5900
John Theurer Cancer Center at the Hackensack University Medical Center The mission of the John...
Click here to add this to my saved trials
