Acute Graft-versus-Host Disease Treatment (BMT CTN 0802)
Immune System Disorders
Drug: Mycophenolate Mofetil
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Multi-Center, Randomized, Double Blind, Phase III Trial Evaluating Corticosteroids With Mycophenolate Mofetil vs. Corticosteroids With Placebo as Initial Systemic Treatment of Acute Graft-Vs-Host-Disease (BMT CTN #0802)|
- GVHD-free Survival [ Time Frame: Day 56 ] [ Designated as safety issue: Yes ]Success is defined as alive and free of GVHD at day 56 after randomization, all others are considered to be a study failure.
- Percentage of Surviving Participants With Complete Response (CR) [ Time Frame: Days 14, 28, and 56 ] [ Designated as safety issue: No ]CR is defined as a score of 0 for the GVHD grading in all evaluable organs.
- Incidence of GVHD Flares Requiring Increased Therapy [ Time Frame: Day 90 ] [ Designated as safety issue: Yes ]Flares are defined as any progression of acute GVHD after an initial response (i.e., earlier CR or PR) that requires re-escalation of steroid dosing, or initiation of additional topical or systemic therapy.
- Incidence of Discontinuation of Immune Suppression Without Flare [ Time Frame: Day 56, Day 180 and Day 360 post-treatment ] [ Designated as safety issue: No ]
- Cumulative Steroid Dose [ Time Frame: Days 28 and 56 ] [ Designated as safety issue: No ]The cumulative steroid dose for each patient will be calculated by adding the doses (end of each week's dose) for each of the first four weeks of treatment, divided by the number of days of survival during this interval. The cumulative steroid dose was calculated for all patients per treatment arm and compared.
- Incidence of Topical/Non-absorbable Therapy [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
- Overall GVHD-free Survival Post-randomization [ Time Frame: Months 6 and 12 ] [ Designated as safety issue: No ]
- Incidence of Chronic GVHD [ Time Frame: 12 months post-randomization ] [ Designated as safety issue: Yes ]
- Incidence of Systemic Infections [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]Number of participants that experienced at least one infection.
- Incidence of Epstein-Barr Virus (EBV)-Associated Lymphoma [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Incidence of Cytomegalovirus (CMV) Reactivation [ Time Frame: Year 1 ] [ Designated as safety issue: Yes ]
- Cumulative Incidence of a Severe/Life-threatening/Fatal Infections [ Time Frame: Year 1 ] [ Designated as safety issue: Yes ]
- Disease-Free Survival (DFS) Post-Randomization [ Time Frame: Year 1 ] [ Designated as safety issue: No ]DFS includes death or progression/relapse of malignancy
- Treatment Related Mortality (TRM) [ Time Frame: Year 1 ] [ Designated as safety issue: Yes ]
- Change in Patient Reported Outcomes From Enrollment to Day 56 [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Corticosteroids with placebo
Oral dosing should be delivered in 250 mg units blinded placebo. For those < 40 kg, IV dosing should be within ± 10% of the exact dose. Intravenous doses are infused over a two-hour period.
Other Name: Inactive drug
Experimental: Mycophenolate Mofetil
Corticosteroids with Mycophenolate Mofetil
Drug: Mycophenolate Mofetil
Oral dosing should be delivered in 250 mg units. For those < 40 kg, IV dosing should be within ± 10% of the exact dose. Intravenous doses are infused over a two-hour period.
Corticosteroids have been used as primary therapy for acute GVHD for many years. Historical published and unpublished data from Johns Hopkins, M. D. Anderson, University of Michigan and others defined an expected 35%-53% complete response (CR) at Day +28 of corticosteroid therapy for previously untreated patients with acute GVHD.
BMT CTN study 0302 (NCT00224874)was a randomized Phase II study evaluating etanercept, mycophenolate mofetil, denileukin diftitox or pentostatin in addition to corticosteroids. The results of that study suggested that mycophenolate mofetil produced the highest rates of CR at Day 28 and overall survival, supporting its evaluation in a Phase III study. Day 56 GVHD-free survival for the four treatment arms (all combining corticosteroids with one of the four study drugs) ranged from 39-71% across the four study arms.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01002742
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|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|