The Use of Etanercept Enbrel as Sole Treatment for Grade I Acute Graft Versus Host Disease
Condition: Acute Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Etanercept (Enbrel)
Intervention description: 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.
Intervention MeSH terms: Etanercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Healthy volunteers: No
Keywords: (GVHD)

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient must have undergone HCT (donor cells from any source) with either a
             myeloablative or nonmyeloablative preparative regimen.

          2. Patient may be any age.

          3. 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.

        Exclusion Criteria:

          1. Patients who are pregnant (positive urine or serum test) or nursing.

          2. Active infections which are unresponsive to antibiotics (> 2 consecutive [at least 24
             hours apart], positive blood cultures after initiation of treatment).

          3. Allergic or otherwise undesirable reaction to etanercept.

          4. 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.

          5. Use of etanercept for any other purpose.

          6. Noncompliance with medications.

          7. Grade II-IV GVHD (history of or at time of study entry).