The Use of Etanercept (Enbrel®) in the Treatment of Acute Graft-Versus-Host Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00141713
Recruitment Status : Completed
First Posted : September 1, 2005
Last Update Posted : March 13, 2013
Information provided by (Responsible Party):
John Levine, MD, University of Michigan Cancer Center

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

Condition or disease Intervention/treatment Phase
Graft-Versus-Host Disease Drug: Etanercept Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Use of Etanercept (Enbrel®) in the Treatment of Acute Graft-Versus-Host Disease
Study Start Date : October 2003
Actual Primary Completion Date : November 2006
Actual Study Completion Date : December 2006

Arm Intervention/treatment
Experimental: 1
etanercept treatment for GVHD
Drug: Etanercept
Patients enrolled on the study will receive etanercept at 0.4 mg/kg per dose up to a maximum of 25 mg per dose subcutaneously twice a week. Etanercept must be initiated within 72 hours of starting solumedrol.

Primary Outcome Measures :
  1. To evaluate the response rate of etanercept when administered with steroids for treatment of biopsy proven aGVHD. [ Time Frame: at 1, 2, and 3 months ]

Secondary Outcome Measures :
  1. 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. [ Time Frame: at 1, 2, and 3 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00141713

United States, Michigan
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Principal Investigator: John E. Levine, MS MD University of Michigan

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: John Levine, MD, Professor of Pediatrics, University of Michigan Cancer Center Identifier: NCT00141713     History of Changes
Other Study ID Numbers: UMCC 3-37
2003-0591 ( Other Identifier: University of Michigan IRBMED )
FD-R-002397-03-2 ( Other Grant/Funding Number: FDA OOPD )
First Posted: September 1, 2005    Key Record Dates
Last Update Posted: March 13, 2013
Last Verified: March 2013

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors