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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)

Phase 2
2 Years
Not Enrolling
Graft vs Host Disease, Immune System Disorders

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Trial Information

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)


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).

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

- ANC greater than 500/┬ÁL

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Complete Response (CR) at Day 28 of Therapy

Outcome Description:

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.

Outcome Time Frame:

Measured at Day 28

Safety Issue:


Principal Investigator

Edward Ball, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Diego


United States: Food and Drug Administration

Study ID:




Start Date:

September 2005

Completion Date:

June 2012

Related Keywords:

  • Graft Vs Host Disease
  • Immune System Disorders
  • Acute Graft vs Host Disease
  • GVHD
  • Graft vs Host Disease
  • Immune System Diseases



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