The Use of Etanercept Enbrel as Sole Treatment for Grade I Acute Graft Versus Host Disease

NCT00726375 | Completed Phase 3 Results DMC

• 2 other identifiers: UMCC 2007.139HUM 17897
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clinical trial to see if treatment with etanercept for early skin graft-versus-host disease (GVHD) can effectively treat and prevent progression of the disease without using high dose steroids. GVHD is a common complication following a bone marrow transplant from another donor. GVHD occurs after transplant, when the donor's blood cells (called lymphocytes) recognize parts of your body, such as the skin, as foreign. A certain chemical, called Tumor Necrosis Factor, or TNF, also causes damage to the skin. The main effect on the skin is a red rash, when the skin GVHD is mild, but in more severe forms the skin can blister. We have been studying GVHD at the University of Michigan for the past decade. We know that high levels of TNF makes GVHD worse. Our research has shown that adding an anti-TNF drug (called etanercept or Enbrel®) to the standard GVHD treatment of high dose steroids leads to improvement in the GVHD in twice as many patients compared to when steroids alone are used. It is now standard practice at the University of Michigan and many other centers to treat GVHD with both steroids and etanercept. The management of early skin GVHD for most patients involves treatment with steroids, given both as a cream and by either the mouth (in pills) or IV. Early skin GVHD is also called grade I GVHD, which means the skin rash covers less than half of the body. Steroid treatment can be effective; however, it also causes many complications such as an increased risk of infection, weight gain, stomach ulcers, muscle weakness and bone damage, among many others. We have developed this study to test whether starting treatment with etanercept and steroid creams alone can treat the GVHD without requiring the use of high dose steroids. The goal is to avoid the complications that come with high dose oral or IV steroid treatment. The high dose steroid treatment would only begin if your GVHD got worse.

Conditions

Acute Graft Versus Host Disease

Keywords

(GVHD)

Outcome Measures

Primary Outcomes (1)

• The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment

  We hypothesized that treatment of grade 1 acute GVHD (Graft Versus Host Disease) with etanercept would reduce the proportion of patients who progressed to grade 2 to 4 acute GVHD within 4 weeks of diagnosis from 58%, historically observed at our institution, to 38%.

  28 days

Secondary Outcomes (1)

• The Number of Patients in Complete Remission (CR) at Four Weeks.

  28 days

Study Arms (1)

Etanercept

EXPERIMENTAL

a maximum of 8 SQ doses of 'Etanercept (Enbrel) at 0.4mg/kg per dose up to a maximum of 25 mg per dose

Drug: Etanercept (Enbrel)

Interventions

Etanercept (Enbrel) DRUG

Etanercept will begin within 72 hours of the diagnosis of Grade I acute GVHD and after consent for this study. Subjects receive eight doses of etanercept over four weeks. All doses will be administered by SQ injection. All subsequent doses will be given as subcutaneous injections into the skin. Injections will be given twice weekly with at least one day in between injections. The injections can be given in clinic, in the hospital, or self administered injections.

Etanercept

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have undergone HCT (donor cells from any source) with either a myeloablative or nonmyeloablative preparative regimen.
• Patient may be any age.
• Patient must have biopsy-proven Grade I acute GVHD (Appendix A). Biopsy report does not have to be back from Pathology prior to enrollment. Patients whose biopsy for GVHD identifies pathology inconsistent with GVHD will be removed from the study and replaced. However, because GVHD is a clinical diagnosis, biopsies which are non-diagnostic or do not show a clear non-GVHD etiology will not be cause to remove the patient from the study.

You may not qualify if:

• Patients who are pregnant (positive urine or serum test) or nursing.
• Active infections which are unresponsive to antibiotics (\> 2 consecutive \[at least 24 hours apart\], positive blood cultures after initiation of treatment).
• Allergic or otherwise undesirable reaction to etanercept.
• Use of any oral or intravenous steroids at any previous time for GVHD treatment. Prior use of steroid therapy (i.e. hydrocortisone) as pre-medication for transfusions is permissible. Prior use of topical steroids is allowed.
• Use of etanercept for any other purpose.
• Noncompliance with medications.
• Grade II-IV GVHD (history of or at time of study entry).

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Gatza E, Braun T, Levine JE, Ferrara JL, Zhao S, Wang T, Chang L, Harris A, Pawarode A, Kitko C, Magenau JM, Yanik GA, Couriel DR, Goldstein S, Connelly J, Reddy P, Paczesny S, Choi SW. Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014 Sep;20(9):1426-34. doi: 10.1016/j.bbmt.2014.05.023. Epub 2014 Jun 2.

  PMID: 24892263 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Limitations and Caveats

Due to difficulties obtaining approval for insurance coverage of the study drug, only 34 of 50 patients were enrolled. The study was terminated prematurely and findings were reported for 34 patients.

Results Point of Contact

• Title: Dr. Sung Choi
• Organization: University of Michigan Comprehensive Cancer Center

sungchoi@umich.edu

734-615-5707

Study Officials

• Sung Choi, MD

  The University of Michigan Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: July 31, 2008
• Study Start: May 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2014
• Last Updated: January 5, 2016
• Results First Posted: August 4, 2014

Record last verified: 2015-12

Locations

US (1)