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



Status:Completed
Conditions:Infectious Disease, Orthopedic, Hematology
Therapuetic Areas:Hematology, Immunology / Infectious Diseases, Orthopedics / Podiatry
Healthy:No
Age Range:2 - Any
Updated:9/27/2017
Start Date:September 2005
End Date:June 2012

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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)

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.

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).

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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
We found this trial at
19
sites
1600 SW Archer Rd # M509
Gainesville, Florida 32610
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Minneapolis, Minnesota 55455
(612) 625-5000
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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1100 Fairview Avenue North
Seattle, Washington 98109
(206) 667-5000
Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of...
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Ann Arbor, Michigan 48109
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Baltimore, Maryland 21287
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Boston, Massachusetts 02114
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1500 East Duarte Road
Duarte, California 91010
626-256-HOPE (4673)
City of Hope National Medical Center City of Hope is dedicated to making a difference...
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Durham, North Carolina 22705
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30 Prospect Ave
Hackensack, New Jersey 07601
(201) 996-2000
Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Emile St
Omaha, Nebraska 68198
(402) 559-4000
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
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Philadelphia, Pennsylvania 19104
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Portland, Oregon 97227
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Saint Louis, Missouri 63110
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San Antonio, Texas 78229
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San Diego, California 92103
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Stanford, California 94305
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