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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Vincent T. Ho, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00053976
First received: February 5, 2003
Last updated: January 19, 2017
Last verified: January 2017
  Purpose

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 Intervention Phase
Graft Versus Host Disease
Biological: Daclizumab
Drug: methylprednisolone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: Treatment of Acute Graft vs. Host Disease With Steroids Plus Daclizumab (Zenapax) or Placebo

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Rate of decrease of acute GVHD grade [ Time Frame: Day 42 ]

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

Enrollment: 105
Study Start Date: January 2001
Study Completion Date: November 2004
Primary Completion Date: November 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053976

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114-2698
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Investigators
Study Chair: Stephanie J. Lee, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Vincent T. Ho, MD, VIncent T. Ho, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00053976     History of Changes
Other Study ID Numbers: 99-279
P30CA016056 ( US NIH Grant/Contract Award Number )
P30CA006516 ( US NIH Grant/Contract Award Number )
RPCI-DS-0218
ROCHE-RPCI-DS-0218
Study First Received: February 5, 2003
Last Updated: January 19, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Dana-Farber Cancer Institute:
graft versus host disease

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Daclizumab
Immunoglobulin G
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on March 29, 2017