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

NCT ID: NCT00053976

Last Updated: 2017-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-01-31
• Study Completion Date: 2004-11-30

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.

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Daclizumab

Intervention Type: BIOLOGICAL

methylprednisolone

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

methylprednisolone

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Interventions

Daclizumab

Intervention Type: BIOLOGICAL

methylprednisolone

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Zenapax

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Vincent T. Ho, MD

VIncent T. Ho, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephanie J. Lee, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Baylor University Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

P30CA016056

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RPCI-DS-0218

Identifier Type: -

Identifier Source: secondary_id

ROCHE-RPCI-DS-0218

Identifier Type: -

Identifier Source: secondary_id

99-279

Identifier Type: -

Identifier Source: org_study_id