Clinical trial NCT00141713: The Use of Etanercept (Enbrel®) in the Treatment of Acute Graft-Versus-Host Disease
Official title: The Use of Etanercept (Enbrel®) in the Treatment of Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft-Versus-Host Disease
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2005-09-01
Enrollment: 40
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Etanercept (Enbrel) will be added to standard therapy for acute Graft-versus-Host Disease to see if the effectiveness of standard therapy can be improved.

Partial Funding Source- FDA OOPD

Detailed description: The standard treatment for acute graft-versus-host disease is a combination of steroids and tacrolimus or cyclosporine. Previous work has shown that less than 50% of patients respond fully to GVHD. Without a good response, patients often have a prolonged treatment for this disease, often involving hospitalization and sometimes even death.

Etanercept is a drug that blocks a chemical called Tumor Necrosis Factor (TNF) from causing damage to tissue. Etanercept (Enbrel) will be added to help improve the response to standard treatment for graft-versus-host disease (GVHD).

This is an experimental research project. It is not known whether the etanercept will actually improve the body's response to graft-versus-host disease. This treatment is meant to determine if etanercept will improve your response to treatment of GVHD.

Eligibility criteria: Inclusion Criteria:

* Patient may be transplanted with stem cells from any source using either a myeloablative or nonmyeloablative preparative regimen
* Patient may be any age
* Patient must have biopsy proven new onset of aGVHD; Clinical Grading must be II-IV and may occur after stem cell transplant or donor leukocyte infusion (DLI). Patients may begin Etanercept treatment prior to biopsy confirmation of GVHD. Acute GVHD will be determined by clinical presentation and not timing from stem cell infusion
* Patient must be on solumedrol at a dose of 2mg/kg/day of actual body weight for no more than 72 hours prior to the initiation of etanercept
* Patient must have evidence of neutrophil engraftment with an ANC of \> 500 for three consecutive days
* Pulse ox \> 90% on room air

Exclusion Criteria:

* Pregnancy or nursing mother
* Intolerance or allergic reaction to etanercept
* Previous use of steroids for treatment of acute GVHD
* Active infection, chronic or localized, not responding to antibiotics, with continued signs of infection (patients with a positive C. Difficile test will not be excluded from the study)
* Condition that might predispose to developing serious infections (i.e. active and uncontrolled diabetes mellitus, sickle cell anemia)
* Other investigational agents for the treatment or prophylaxis of graft-vs-host disease within the past 2 weeks
* Serum creatinine \> 2.0mg/dl
* Patients being treated for acute pulmonary dysfunction (IPS) study using etanercept
* Patients with hypotension believed to be secondary to sepsis syndrome or heart failure requiring \> 1 inotropic agent, or dopamine \>5mcg/kg/minute for blood pressure support
* Evidence of congestive heart failure on clinical exam
* Evidence of hepatic dysfunction with an ALT or AST \> 2.5 x ULN, not due to GVHD

Primary outcomes:
measure: To evaluate the response rate of etanercept when administered with steroids for treatment of biopsy proven aGVHD.
timeFrame: at 1, 2, and 3 months
Secondary outcomes:
measure: To analyze intracellular cytokine levels, lymphocyte phenotype and plasma cytokine levels in patients with aGVHD before and after treatment with etanercept and to correlate these laboratory endpoints with clinical outcomes during the trial.
timeFrame: at 1, 2, and 3 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: The University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: John E. Levine, MS MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levine JE, Paczesny S, Mineishi S, Braun T, Choi SW, Hutchinson RJ, Jones D, Khaled Y, Kitko CL, Bickley D, Krijanovski O, Reddy P, Yanik G, Ferrara JL. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008 Feb 15;111(4):2470-5. doi: 10.1182/blood-2007-09-112987. Epub 2007 Nov 27.