A Multi-Center, Randomized, Double Blind, Phase III Trial Evaluating Corticosteroids With Mycophenolate Mofetil vs. Corticosteroids With Placebo as Initial Systemic Treatment of Acute GVHD (BMT CTN 0802)

Inclusion Criteria:

- Acute GVHD developing after allogeneic hematopoietic stem cell transplant using
either bone marrow, peripheral blood stem cells or cord blood. Recipients of
non-myeloablative and myeloablative transplants are eligible.

- Acute GVHD after planned donor lymphocyte infusion or planned T cell addback are
eligible.

- De novo acute GVHD requiring systemic therapy. GVHD is defined as the presence of
skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis
presenting in a context in which acute GVHD is likely to occur and where other
etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are
unlikely or have been ruled out. Note that patients with stage I and II skin only
(overall grade I) or isolated upper gastrointestinal (GI) involvement are eligible if
the treating physician deems that systemic high-dose corticosteroid treatment is
indicated.

- The patient must have had no previous systemic immune suppressive therapy for
treatment of acute GVHD except for a maximum 72 hours of prior corticosteroid therapy
at >0.5mg/kg methylprednisolone or equivalent after the onset of acute GVHD.

- Clinical status at enrollment to allow tapering of steroids to not less than 0.25
mg/kg/day prednisone (0.2 mg/kg/day methylprednisolone) at Day 28 of therapy.

- Absolute neutrophil count (ANC) greater than 500/µL.

- Written informed consent and/or assent from patient, parent or guardian.

- Documentation that the assent document and education materials have been provided to,
and reviewed with, patients between the ages of 7 and 17.

- Patients of all ages are eligible.

- Biopsy confirmation of GVHD is recommended, but not required. Enrollment should not
be delayed for biopsy or pathology results unless these are to be used to decide
about whether to treat for GVHD.

Exclusion Criteria:

- Patients receiving mycophenolate mofetil or mycophenolic acid (Myfortic) within seven
days of screening for enrollment.

- Patients with uncontrolled infections will be excluded. If a bacterial or viral
infection is present, patients must be receiving definitive therapy and have no signs
of progressing infection for 72 hours prior to enrollment. If a fungal infection is
present, patients must be receiving definitive systemic anti-fungal therapy and have
no signs of progressing infection for 1 week prior to enrollment. Progressing
infection is defined as hemodynamic instability attributable to sepsis or new
symptoms, worsening physical signs or radiographic findings attributable to
infection. Persisting fever without other signs or symptoms will not be interpreted
as progressing infection.

- Relapsed/persistent malignancy requiring rapid immune suppression withdrawal.

- Patients with GVHD after an unplanned DLI, i.e., DLI that was not part of their
original transplant therapy plan, or DLI given for treatment of persistent or
recurrent malignancy after transplantation.

- Patients unlikely to be available at the transplantation center on Day 28 and 56 of
therapy.

- A clinical syndrome resembling de novo chronic GVHD developing at any time after
allotransplantation.

- Patients receiving other drugs for the treatment of GVHD.

- Patients receiving methylprednisolone > 0.5 mg/kg/day (or 0.6 mg/kg/day prednisone)
within 7 days before the onset of acute GVHD. If steroid therapy has been
administered for treatment of a non-GVHD related condition and tapered to ≤ 0.5
mg/kg/day methylprednisolone (0.6 mg/kg/day prednisone) for seven or more days before
the onset of acute GVHD, the patient is eligible.

- Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use
effective birth control for the duration of the study. Available evidence and/or
expert consensus is inconclusive or is inadequate for determining infant risk when
used during breastfeeding, therefore breast feeding patients are not eligible.

- Adults unable to provide informed consent.

- Patients on dialysis.

- Patients with severe hepatic VOD or sinusoidal obstruction syndrome who in the
judgement of the treating physician are not expected to have normalized bilirubin by
Day 56 after enrollment.

- Patients with a history of intolerance/allergy to MMF.