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

Sponsor

Dana-Farber Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00053976

Collaborator

National Cancer Institute (NCI) (NIH)

105

Enrollment

Locations

Arms

Duration (Months)

13.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Biological: Daclizumab Drug: methylprednisolone Drug: Placebo	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2001

Actual Primary Completion Date :

Nov 1, 2003

Actual Study Completion Date :

Nov 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daclizumab 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 Other Names: Zenapax Drug: methylprednisolone
Placebo Comparator: Placebo 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 Drug: Placebo

Arm

Intervention/Treatment

Experimental: Daclizumab

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

Other Names:

Zenapax

Drug: methylprednisolone

Placebo Comparator: Placebo

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

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Rate of decrease of acute GVHD grade [Day 42]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114-2698
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
5	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
7	Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
8	Baylor University Medical Center	Dallas	Texas	United States	75246