Clinical trial NCT00726375: The Use of Etanercept Enbrel as Sole Treatment for Grade I Acute Graft Versus Host Disease
Official title: The Use of Etanercept (Enbrel) as Sole Treatment for Grade I Acute Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Graft Versus Host Disease
Keywords: (GVHD)
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2008-07-31
Enrollment: 34
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment
timeFrame: 28 days
Secondary outcomes:
measure: The Number of Patients in Complete Remission (CR) at Four Weeks.
timeFrame: 28 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: The University of Michigan Comprehensive Cancer Center
name: Sung Choi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.