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)
4 other identifiers
interventional
180
1 country
19
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2005
Longer than P75 for phase_2
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2005
CompletedFirst Submitted
Initial submission to the registry
September 21, 2005
CompletedFirst Posted
Study publicly available on registry
September 23, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2009
CompletedResults Posted
Study results publicly available
April 9, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2012
CompletedNovember 1, 2021
August 1, 2017
3.3 years
September 21, 2005
January 29, 2010
October 19, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Complete Response (CR) at Day 28 of Therapy
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.
Measured at Day 28
Secondary Outcomes (8)
Number of Partial Response (PR), Mixed Response (MR), and Progression
Measured at Day 28
Proportion of Treatment Failure
Measured at Day 56
Number of Patients With Acute Graft-versus-host Disease (GVHD) Flares at Day 90
Measured at Day 90
Number of Patients Discontinuing Immune Suppression Without Flare
Measured at Days 90, 180, and 270 post-treatment
Number of Patients With Chronic Graft-versus-host Disease (GVHD)
Measured at 9 months
- +3 more secondary outcomes
Study Arms (4)
Etanercept
EXPERIMENTALEnroll within 48 hours of new onset acute GVHD and randomize to Etanercept
Mycophenolate Mofetil
EXPERIMENTALEnroll within 48 hours of new onset acute GVHD and randomize to Mycophenolate Mofetil
Denileukin Diftitox
EXPERIMENTALEnroll within 48 hours of new onset acute GVHD and randomize to Denileukin Diftitox
Pentostatin
EXPERIMENTALEnroll within 48 hours of new onset acute GVHD and randomize to Pentostatin
Interventions
Etanercept \[25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks\].
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 (ONTAK®) \[9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19\].
Pentostatin \[1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17
Eligibility Criteria
You may qualify if:
- Prior allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells, or cord blood
- 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
You may not qualify if:
- ONTAK, pentostatin, or etanercept given within 7 days of enrollment
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
City of Hope National Medical Center
Duarte, California, 91010, United States
University of California
San Diego, California, 92093, United States
Stanford Hospital and Clinics
Stanford, California, 94305, United States
University of Florida College of Medicine (Shands)
Gainesville, Florida, 32610, United States
Johns Hopkins/SKCCC
Baltimore, Maryland, 21231, United States
DFCI/Brigham & Women's Hospital
Boston, Massachusetts, 02114, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Washington University/Barnes Jewish Hospital
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021, United States
Duke University Medical Center (Peds)
Durham, North Carolina, 27705, United States
University Hospitals of Cleveland/Case Western
Cleveland, Ohio, 44106, United States
Oregon Health Sciences University
Portland, Oregon, 97239, United States
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, 19104, United States
University of Texas/MD Anderson CRC
Houston, Texas, 77030, United States
Texas Transplant Institute
San Antonio, Texas, 78229, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Related Publications (4)
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.
PMID: 19443659RESULTJacobson 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.
PMID: 19925875RESULTLevine 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.
PMID: 20541024RESULTLevine 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.
PMID: 22383800DERIVED
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Corporation
Study Officials
- STUDY DIRECTOR
Mary Horowitz, MD
Center for International Blood and Marrow Transplant Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 21, 2005
First Posted
September 23, 2005
Study Start
September 1, 2005
Primary Completion
January 1, 2009
Study Completion
June 1, 2012
Last Updated
November 1, 2021
Results First Posted
April 9, 2010
Record last verified: 2017-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Within 6 months of official study closure at participating sites.
- Access Criteria
- Available to the public
Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).