Natalizumab and Prednisone or Methylprednisolone in Treating Participants with High Risk Acute Graft-Versus-Host Disease

Inclusion Criteria

• New onset acute GVHD Ann Arbor score 2 or 3 following allogeneic bone marrow transplantation (BMT); any clinical severity (Glucksberg grade I-IV) is eligible; patients with prior or existing diagnosis of GVHD without any treatment are eligible; patients given only topical corticosteroids for skin GVHD are eligible
• Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood); recipients of non-myeloablative and myeloablative transplants are eligible
• No prior systemic treatment for acute GVHD except for a maximum of 3 days of prednisone (or IV methylprednisolone) =< 2 mg/kg/day; topical skin steroid treatment, non-absorbable oral steroid treatment for gastrointestinal (GI) GVHD, and resumption of GVHD prophylaxis agents (e.g., calcineurin inhibitors) are permissible; patients enrolled in BMT CTN 1501 who randomized to sirolimus are also eligible; exceptions can be made on a case-by-case basis with sponsor-investigator approval
• Direct bilirubin must be < 2 mg/dL unless the elevation is known to be due to Gilbert's syndrome or acute GVHD (aGVHD) within 3 days of enrollment
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) must be < 5 x the upper limit of the normal range within 3 days of enrollment unless the elevation is due to liver GVHD
• If the patient is a woman of child-bearing potential, the patient and their sexual partner must agree to practice effective contraception
• Written informed consent from patient or legal representative
• Biopsy of acute GVHD target organ is strongly recommended but not required; enrollment should not be delayed for biopsy or pathology results; patients who do not enroll within 3 days of initiation of systemic steroid treatment for acute GVHD are not permitted to participate

Exclusion Criteria

• Patients with malignancy that is suspected or proven to have progressed, relapsed, or be persistent since progressive, relapsed or persistent malignancy documented since BMT
• Uncontrolled active infection
• Patients with chronic GVHD only; patients diagnosed with overlap syndrome are still eligible
• History of or current diagnosis of progressive multifocal leukoencephalopathy (PML)
• Known hypersensitivity to natalizumab
• Pregnant or nursing (lactating) women
• Use of other drugs for the treatment of acute GVHD
• Steroid therapy for indications other than GVHD at doses > 0.5 mg/kg/d of methylprednisolone or equivalent within 7 days prior to initiation of GVHD treatment
• Patients on dialysis
• Patients requiring ventilator support
• Investigational agent within 30 days of enrollment without approval from the sponsor- principal investigator (PI)
• History of allergic reaction to natalizumab