Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
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|ClinicalTrials.gov Identifier: NCT00224874|
Recruitment Status : Completed
First Posted : September 23, 2005
Results First Posted : April 9, 2010
Last Update Posted : September 25, 2017
|Condition or disease||Intervention/treatment||Phase|
|Graft vs Host Disease Immune System Disorders||Drug: Etanercept Drug: Mycophenolate Mofetil Drug: Denileukin Diftitox Drug: Pentostatin||Phase 2|
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.
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||180 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Study Start Date :||September 2005|
|Actual Primary Completion Date :||January 2009|
|Actual Study Completion Date :||June 2012|
Enroll within 48 hours of new onset acute GVHD and randomize to Etanercept
Etanercept [25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks].
Other Name: ENBREL®
Experimental: Mycophenolate Mofetil
Enroll within 48 hours of new onset acute GVHD and randomize to Mycophenolate Mofetil
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].
Other Name: CellCept®
Experimental: Denileukin Diftitox
Enroll within 48 hours of new onset acute GVHD and randomize to Denileukin Diftitox
Drug: Denileukin Diftitox
Denileukin Diftitox (ONTAK®) [9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19].
Other Name: ONTAK®
Enroll within 48 hours of new onset acute GVHD and randomize to Pentostatin
Pentostatin [1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17
Other Name: Nipent®
- Number of Complete Response (CR) at Day 28 of Therapy [ Time Frame: Measured at Day 28 ]Complete response at day 28 after randomization. CR was defined as resolution of all signs and symptoms of Graft-Versus-Host Disease (GVHD) in all evaluable organs in comparison to Day 1 scoring.
- Number of Partial Response (PR), Mixed Response (MR), and Progression [ Time Frame: Measured at Day 28 ]Partial response, mixed response, and progression at Day 28 after randomization. Partial response was defined as improvement in one or more organs involved with Graft-Versus-Host Disease (GVHD) symptoms without progression in others. Mixed response was defined as improvement in one or more organs with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ. Progression was defined as deterioration in at least one organ without any improvement in others.
- Proportion of Treatment Failure [ Time Frame: Measured at Day 56 ]
- Number of Patients With Acute Graft-versus-host Disease (GVHD) Flares at Day 90 [ Time Frame: Measured at Day 90 ]Flares were defined as any increase in symptoms of or therapy for acute GVHD after an initial response (i.e., progression from an earlier CR or PR).
- Number of Patients Discontinuing Immune Suppression Without Flare [ Time Frame: Measured at Days 90, 180, and 270 post-treatment ]Immunosuppression discontinuation was defined as the discontinuation of corticosteroids and all additional immunosuppressives, except cyclosporine or tacrolimus, for treatment of acute GVHD without subsequent flare by Day 90 post-initiation of therapy and later by discontinuation of all immunosuppressive medications, including cyclosporine or tacrolimus.
- Number of Patients With Chronic Graft-versus-host Disease (GVHD) [ Time Frame: Measured at 9 months ]Number of patients with limited and extensive chronic GVHD at 9 months
- Number of Patients Surviving at 6 and 9 Months Post Randomization [ Time Frame: Measured at 6 and 9 months ]
- Cumulative Incidence of Systemic Infections [ Time Frame: Measured at Day 270 ]
- Incidence of Epstein-Barr Virus (EBV)-Associated Lymphoma [ Time Frame: Measured at 9 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00224874
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|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|