NCT00224874

Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)

Initial Systemic Treatment of Acute GVHD: A Phase II Randomized Trial Evaluating Etanercept, Mycophenolate Mofetil (MMF), Denileukin Diftitox (ONTAK), and Pentostatin in Combination With Corticosteroids (BMT CTN #0302)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (actual)
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) · NIH
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

Summary

The study is a randomized Phase II, four arm treatment trial. The primary purpose of the study is to define new agents with promising activity against acute graft-versus-host disease (GVHD) suitable for testing against corticosteroids alone in a subsequent Phase III trial.

Detailed description

BACKGROUND: Acute graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell (HSC) transplantation. Acute GVHD produces significant morbidity and complicates patient management resulting in organ toxicity, frequent infections, malnutrition, and substantial delay in recovery from transplantation. Corticosteroids have been the primary therapy for acute GVHD for over three decades. Various additional immunosuppressive strategies have been tested as GVHD therapy but neither anti-thymocyte globulin (ATG), CD5-immunotoxins, IL-1 antagonists nor other agents have been demonstrably helpful in either control of GVHD symptoms or improvement in survival. Published response rates of complete response (CR) to acute GVHD therapy with corticosteroids range from 25-41%. These rates will be used as benchmarks for assessing efficacy of promising new agents. New immunosuppressive agents and strategies are required to improve the management of GVHD and decrease the toxicities of the immunosuppressive regimens. DESIGN NARRATIVE: In this trial, patients with newly diagnosed acute GVHD will be randomly assigned to receive corticosteroids plus one of four new agents (etanercept, MMF, denileukin diftitox \[Ontak\], and pentostatin). A control arm of only corticosteroids will not be employed. Each agent will be assessed for safety and efficacy (at least 35% complete remission \[CR\] rate at Day 28 of therapy can be expected from previously untreated patients).

Conditions

• Graft vs Host Disease
• Immune System Disorders

Interventions

Type	Name	Description
DRUG	Etanercept	Etanercept \[25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks\].
DRUG	Mycophenolate Mofetil	Mycophenolate mofetil (MMF) \[20 mg/kg (maximum 1 gm) orally or intravenously twice daily; continue through prednisone taper, then taper MMF over 4 weeks\].
DRUG	Denileukin Diftitox	Denileukin Diftitox (ONTAK®) \[9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19\].
DRUG	Pentostatin	Pentostatin \[1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17

Timeline

• Start date: 2005-09-01
• Primary completion: 2009-01-01
• Completion: 2012-06-01
• First posted: 2005-09-23
• Last updated: 2021-11-01
• Results posted: 2010-04-09

Locations

19 sites across 1 country: United States