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)

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/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