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

January 19, 2017 updated by: Vincent T. Ho, MD, Dana-Farber Cancer Institute

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

105

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114-2698
        • Massachusetts General Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Cancer Institute at Oregon Health and Science University
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.
Drug: methylprednisolone
Biological: Daclizumab
Other Names:
  • Zenapax
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: Placebo
Drug: methylprednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of decrease of acute GVHD grade
Time Frame: Day 42
Day 42

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Stephanie J. Lee, MD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Primary Completion (Actual)

November 1, 2003

Study Completion (Actual)

November 1, 2004

Study Registration Dates

First Submitted

February 5, 2003

First Submitted That Met QC Criteria

February 5, 2003

First Posted (Estimate)

February 6, 2003

Study Record Updates

Last Update Posted (Estimate)

January 23, 2017

Last Update Submitted That Met QC Criteria

January 19, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 99-279
  • P30CA006516 (U.S. NIH Grant/Contract)
  • P30CA016056 (U.S. NIH Grant/Contract)
  • RPCI-DS-0218
  • ROCHE-RPCI-DS-0218

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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