Acute Graft-versus-Host Disease Treatment (BMT CTN 0802)
Condition: Graft-versus-Host Disease; Immune System Disorders
MeSH terms: Graft vs Host Disease; Immune System Diseases
Intervention: Mycophenolate Mofetil; Placebo
Intervention description: Oral dosing should be delivered in 250 mg units. For those < 40 kg, IV dosing should be within ± 10% of the exact dose. Intravenous doses are infused over a two-hour period.
Patients who weight > 60 kg should receive MMF 1 gm PO/IV every 8 hours.
Patients who weight between 40-60 kg should receive 750 mg PO/IV every 8 hours.
Patients who weight <40 kg should receive 20 mg/kg IV or PO every 8 hours.; Oral dosing should be delivered in 250 mg units blinded placebo. For those < 40 kg, IV dosing should be within ± 10% of the exact dose. Intravenous doses are infused over a two-hour period.
Patients who weight > 60 kg should receive placebo 1 gm PO/IV every 8 hours.
Patients who weight between 40-60 kg should receive 750 mg PO/IV every 8 hours.
Patients who weight <40 kg should receive 20 mg/kg IV or PO every 8 hours.
Intervention MeSH terms: Mycophenolic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 236.0
Sex: All
Healthy volunteers: No
Keywords: GVHD

Summary:

      The study is a Phase III, randomized double blind, placebo controlled, and trial evaluating
      the addition of Mycophenolate mofetil (MMF) vs. placebo to systemic corticosteroids as
      initial therapy for acute Graft Vs Host Disease (GVHD). The primary endpoint will be GVHD
      free survival at Day 56 post randomization.
    

Eligibility criteria:

        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 add back 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 Donor Lymphocyte Infusion (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 Veno-Occlusive Disease (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.