Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
NCT ID: NCT00224874
Last Updated: 2021-11-01
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
180 participants
INTERVENTIONAL
2005-09-30
2012-06-30
Brief Summary
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Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Etanercept
Enroll within 48 hours of new onset acute GVHD and randomize to Etanercept
Etanercept
Etanercept \[25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks\].
Mycophenolate Mofetil
Enroll within 48 hours of new onset acute GVHD and randomize to Mycophenolate Mofetil
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) \[20 mg/kg (maximum 1 gm) orally or intravenously twice daily; continue through prednisone taper, then taper MMF over 4 weeks\].
Denileukin Diftitox
Enroll within 48 hours of new onset acute GVHD and randomize to Denileukin Diftitox
Denileukin Diftitox
Denileukin Diftitox (ONTAK®) \[9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19\].
Pentostatin
Enroll within 48 hours of new onset acute GVHD and randomize to Pentostatin
Pentostatin
Pentostatin \[1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17
Interventions
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Etanercept
Etanercept \[25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks\].
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) \[20 mg/kg (maximum 1 gm) orally or intravenously twice daily; continue through prednisone taper, then taper MMF over 4 weeks\].
Denileukin Diftitox
Denileukin Diftitox (ONTAK®) \[9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19\].
Pentostatin
Pentostatin \[1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* De novo acute GVHD diagnosed within 48 hours prior to enrollment; biopsy confirmation of GVHD is strongly recommended but not required; enrollment should not be delayed awaiting biopsy or pathology results; the patient must have had no previous systemic immune suppressive therapy given for treatment of acute GVHD except for a maximum 48 hours of prior corticosteroid therapy (at least 1 mg/kg/day methylprednisolone)
* Patients that have undergone a scheduled donor lymphocyte infusion (DLI) as part of their original transplant therapy plan
* Absolute neutrophil count (ANC) greater than 500/µL
* Clinical status at enrollment to allow tapering of steroids to not less than 1 mg/kg/day methylprednisolone (1.4 mg/kg/day prednisone) at Day 28 of therapy (e.g., persisting malignant disease suggesting the need for accelerated taper of immunosuppression)
* Estimated creatinine clearance greater than 30 mL/minute
* Assent and educational materials provided to, and reviewed with, patients under the age of 18
Exclusion Criteria
* Active uncontrolled infection
* Patients that have undergone an unscheduled DLI, or DLI that was not part of their original transplant therapy plan
* If any prior steroid therapy (for indication other than GVHD), treatment at doses of at least 0.5 mg/kg/day methylprednisolone within 7 days prior to onset of GVHD
* Patients unlikely to be available at the transplant center on Day 28 and 56 of therapy
* A clinical syndrome resembling de novo chronic GVHD developing at any time after allotransplantation (see Chapter 2 of the BMT CTN Manual of Procedures for details of de novo chronic GVHD)
* Other investigational therapeutics for GVHD within 30 days, including agents used for GVHD prophylaxis
* Patients who are pregnant, breast feeding, or if sexually active, unwilling to use effective birth control for the duration of the study
* Adults unable to provide informed consent
* Patients with a history of intolerance to any of the study drugs
2 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Blood and Marrow Transplant Clinical Trials Network
NETWORK
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Responsible Party
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Principal Investigators
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Mary Horowitz, MD
Role: STUDY_DIRECTOR
Center for International Blood and Marrow Transplant Research
Locations
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City of Hope National Medical Center
Duarte, California, United States
University of California
San Diego, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
University of Florida College of Medicine (Shands)
Gainesville, Florida, United States
Johns Hopkins/SKCCC
Baltimore, Maryland, United States
DFCI/Brigham & Women's Hospital
Boston, Massachusetts, United States
University of Michigan Medical Center
Ann Arbor, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Washington University/Barnes Jewish Hospital
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Duke University Medical Center (Peds)
Durham, North Carolina, United States
University Hospitals of Cleveland/Case Western
Cleveland, Ohio, United States
Oregon Health Sciences University
Portland, Oregon, United States
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States
University of Texas/MD Anderson CRC
Houston, Texas, United States
Texas Transplant Institute
San Antonio, Texas, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Countries
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References
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Alousi AM, Weisdorf DJ, Logan BR, Bolanos-Meade J, Carter S, Difronzo N, Pasquini M, Goldstein SC, Ho VT, Hayes-Lattin B, Wingard JR, Horowitz MM, Levine JE; Blood and Marrow Transplant Clinical Trials Network. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. 2009 Jul 16;114(3):511-7. doi: 10.1182/blood-2009-03-212290. Epub 2009 May 14.
Jacobson PA, Huang J, Wu J, Kim M, Logan B, Alousi A, Grimley M, Bolanos-Meade J, Ho V, Levine JE, Weisdorf D. Mycophenolate pharmacokinetics and association with response to acute graft-versus-host disease treatment from the Blood and Marrow Transplant Clinical Trials Network. Biol Blood Marrow Transplant. 2010 Mar;16(3):421-9. doi: 10.1016/j.bbmt.2009.11.010.
Levine JE, Logan B, Wu J, Alousi AM, Ho V, Bolanos-Meade J, Weisdorf D; Blood and Marrow Transplant Clinical Trials Network. Graft-versus-host disease treatment: predictors of survival. Biol Blood Marrow Transplant. 2010 Dec;16(12):1693-9. doi: 10.1016/j.bbmt.2010.05.019. Epub 2010 Jun 9.
Levine JE, Logan BR, Wu J, Alousi AM, Bolanos-Meade J, Ferrara JL, Ho VT, Weisdorf DJ, Paczesny S. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012 Apr 19;119(16):3854-60. doi: 10.1182/blood-2012-01-403063. Epub 2012 Mar 1.
Provided Documents
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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form
Other Identifiers
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BMT CTN 0302
Identifier Type: OTHER
Identifier Source: secondary_id
285
Identifier Type: OTHER
Identifier Source: secondary_id
BMTCTN0302
Identifier Type: -
Identifier Source: org_study_id
NCT00253656
Identifier Type: -
Identifier Source: nct_alias
NCT00474149
Identifier Type: -
Identifier Source: nct_alias