Methylprednisolone With or Without Daclizumab in Treating Patients With Acute Graft-Versus-Host Disease

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of IL2 receptor antibody (also known as Daclizumab or Zenapax) and corticosteroids alone for control of GVHD. Treatment with corticosteroids is standard care for GVHD. This research is being done because the investigators do not know whether addition of this new medication to standard corticosteroid therapy improves response rates. Since Zenapax binds to a type of cell which is thought to cause GVHD and possibly inactivates them, investigators have reason to believe that addition of Zenapax night result in better control of GVHD This study will determine whether the addition of another medication, Zenapax, will be more effective than steroids alone in suppressing GVHD and improving symptoms of GVHD. Daclizumab (Zenapax) is approved by the Food and Drug Administration (FDA) for use in patient with kidney transplant to help prevent graft rejection. This medication has been used in bone marrow transplant patients to treat GVHD.

Detailed Description
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GVHD occurs when the donor's immune system recognizes a patient's body as foreign and reacts against it. GVHD may result in skin rashes and blistering, liver inflammation and gastrointestinal problems including nausea, vomiting, diarrhea and bleeding. Mild GVHD may be treated with topical medications applied to the skin. More severe GVHD requires medications given intravenously (by vein) or taken by mouth. Steroids are usually given first to treat GVHD but only 40% of people respond to this alone. OBJECTIVES: Compare response to treatment in patients with acute graft-versus-host disease (GVHD) treated with methylprednisolone with or without daclizumab. Compare differences in total methylprednisolone dose and complications in patients treated with these regimens. Compare mortality, days of antibiotics and antifungal therapy, and required hospital days within the first 100 days for patients treated with these regimens. Compare overall survival and incidence of chronic GVHD at 1 year in patients treated with these regimens. OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to prior graft-versus-host disease (GVHD) prophylaxis (immunosuppressive therapy vs T-cell depletion), GVHD organ manifestation (skin only vs other), donor type (6/6 matched sibling vs other), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive methylprednisolone or equivalent corticosteroid IV or orally and daclizumab IV over 15 minutes on days 0, 3, 7, 14, and then weekly as indicated until day 100. Arm II: Patients receive methylprednisolone or equivalent corticosteroid as in arm I and placebo. Patients are followed at 1 year and then annually thereafter.

Official Title
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Treatment of Acute Graft vs. Host Disease With Steroids Plus Daclizumab (Zenapax) or Placebo

Conditions
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Graft Versus Host Disease

Intervention / Treatment
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* Biological: Daclizumab
* Drug: methylprednisolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Allogeneic Transplantation Acute GVHD requiring therapy (skin stage 2 or overall grade II-IV) Signed, informed consent Exclusion Criteria Mental or emotional contraindications as determined by patient's physician Steroids given prophylactically or therapeutically at a dose > 1 mg/kg/d methylprednisolone (including prevention of acute GVHD or treatment for diffuse alveolar hemorrhage and severe obstructive mucositis within 7 days prior to starting acute GVHD therapy. Steroids administered as amphotericin premedication are allowed if below 1 mg/kg/day. Acute GVHD diagnosed solely by virtue of upper GI GVHD Hypersensitivity to Daclizumab or prior therapy with Daclizumab GVHD from donor lymphocyte infusion Other investigational therapeutics within 30 days of enrollment Pregnancy or of fertile, failure to agree to use contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclizumab<br>Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive methylprednisolone or equivalent corticosteroid IV or orally Daclizumab IV on days 0, 3, 7, 14, and then weekly as indicated until day 100. Arm II: Patients receive methylprednisolone or equivalent corticosteroid as in arm I and placebo. Patients are followed at 1 year and then annually thereafter. | Biological: Daclizumab<br> <br> * Other names: Zenapax;Drug: methylprednisolone<br> <br> |
| Placebo Comparator: Placebo<br>Patients are randomized to 1 of 2 treatment arms. Patients receive methylprednisolone or equivalent corticosteroid as in Daclizumab arm Placebo IV on days 0, 3, 7, 14, and then weekly as indicated until day 100. | Drug: methylprednisolone<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decrease of acute GVHD grade |  | Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 100 Day Mortality |  | 100 Day | 
| Complete Response of GVHD |  | 100 Days | 
| Total Days of Antibiotic or Antifungal |  | 100 Days | 
| Number of Hospitalized Days |  | 100 Days | 
| Total Steroid Dose |  | 100 Days | 
| Number of Participants with Steroid related Complication |  | 1 Year | 
| Overall Survival |  | 100 Days | 
| Relapse Rate |  | 1 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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graft versus host disease