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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Levine, MD, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00141713
First received: August 30, 2005
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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 Intervention Phase
Graft-Versus-Host Disease
Drug: Etanercept
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Use of Etanercept (Enbrel®) in the Treatment of Acute Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: October 2003
Study Completion Date: December 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00141713

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

No publications provided

Responsible Party: John Levine, MD, Professor of Pediatrics, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00141713     History of Changes
Other Study ID Numbers: UMCC 3-37, 2003-0591, FD-R-002397-03-2
Study First Received: August 30, 2005
Last Updated: March 12, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
TNFR-Fc fusion protein
Immunoglobulin G
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014