Acute Graft Versus Host Disease
Conditions
Keywords
(GVHD)
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.
Interventions
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.
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment | 28 days | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients in Complete Remission (CR) at Four Weeks. | 28 days | Estimate the proportion of patients in complete remission (CR) at four weeks who remain alive and never require additional therapy four weeks after the last dose of etanercept. Complete remission is defined as the resolution of all manifestations of GVHD (Graft Versus Host Disease) within the first four weeks of treatment. All organs must have a Grade 0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etanercept a maximum of 8 SQ doses of 'Etanercept (Enbrel) at 0.4mg/kg per dose up to a maximum of 25 mg per dose
Etanercept (Enbrel): 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. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Etanercept |
|---|---|
| Age, Continuous | 51 years |
| CMV Status R-, D+ | 3 participants |
| CMV Status R+, D- | 12 participants |
| CMV Status R+, D+ | 9 participants |
| CMV Status Recipient and donor negative | 10 participants |
| Diagnosis Acute lymphoblastic leukemia | 6 participants |
| Diagnosis Acute myelogenous leukemia | 13 participants |
| Diagnosis Chronic lymphocytic leukemia | 1 participants |
| Diagnosis Chronic myelogenous leukemia | 0 participants |
| Diagnosis Multiple myeloma | 4 participants |
| Diagnosis Myelodysplastic syndrome | 4 participants |
| Diagnosis Myelofibrosis | 2 participants |
| Diagnosis Non-Hodgkin's lymphoma | 2 participants |
| Diagnosis Nonmalignant disease | 2 participants |
| Disease Risk Status High | 16 participants |
| Disease Risk Status Intermediate | 5 participants |
| Disease Risk Status Low | 13 participants |
| Donor Matched related | 12 participants |
| Donor Matched unrelated | 16 participants |
| Donor Mismatched related | 0 participants |
| Donor Mismatched unrelated | 6 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants |
| Race/Ethnicity, Customized Other | 4 participants |
| Race/Ethnicity, Customized White | 30 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 34 |
| serious Total, serious adverse events | 3 / 34 |
Outcome results
Primary
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%.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept | The Percentage of Patients Who Progress Within 28 Days of Initiation of Etanercept Treatment | 29 percentage of patients |
Secondary
The Number of Patients in Complete Remission (CR) at Four Weeks.
Estimate the proportion of patients in complete remission (CR) at four weeks who remain alive and never require additional therapy four weeks after the last dose of etanercept. Complete remission is defined as the resolution of all manifestations of GVHD (Graft Versus Host Disease) within the first four weeks of treatment. All organs must have a Grade 0.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept | The Number of Patients in Complete Remission (CR) at Four Weeks. | 14 patients |