Clinical trial NCT00053976: Methylprednisolone With or Without Daclizumab in Treating Patients With Acute Graft-Versus-Host Disease
Official title: Treatment of Acute Graft vs. Host Disease With Steroids Plus Daclizumab (Zenapax) or Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graft Versus Host Disease
Keywords: graft versus host disease
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-02-06
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of decrease of acute GVHD grade
timeFrame: Day 42
Secondary outcomes:
measure: 100 Day Mortality
timeFrame: 100 Day
measure: Complete Response of GVHD
timeFrame: 100 Days
measure: Total Days of Antibiotic or Antifungal
timeFrame: 100 Days
measure: Number of Hospitalized Days
timeFrame: 100 Days
measure: Total Steroid Dose
timeFrame: 100 Days
measure: Number of Participants with Steroid related Complication
timeFrame: 1 Year
measure: Overall Survival
timeFrame: 100 Days
measure: Relapse Rate
timeFrame: 1 Years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Cancer Institute at Oregon Health and Science University
state: Oregon
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Stephanie J. Lee, MD
role: STUDY_CHAIR
References: