Clinical trial NCT01453140: In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus
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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Graft Versus Host Disease
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
First posted: 2011-10-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 28 days to 100 days post transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
Study officials:
affiliation: Hackensack Meridian Health
name: Michele Donato, MD
role: PRINCIPAL_INVESTIGATOR
References: