Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease
Condition: Acute Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: natalizumab; steroids
Intervention description: Natalizumab 300mg on days 0 and 14.; Prednisone 2mg/kg/d (or methyl-prednisolone IV equivalent)
Intervention MeSH terms: Prednisone; Methylprednisolone; Natalizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Graft vs Host Disease; Graft vs Host Reaction; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; adverse effects

Summary:

      This research trial is designed to study the safety and effectiveness of combining the study
      drug, Natalizumab (Tysabri®) with the standard treatment, the use of steroids, as a new
      treatment for acute graft versus host disease (acute GVHD). GVHD is the most common serious
      complication, after bone marrow transplant. GVHD occurs when the donor cells (the graft),
      treat the recipient's body as "foreign" and attack the cells in the recipient's body. During
      this immune system response, donor cells damage body tissues, such as the skin, liver,
      stomach, and/or intestines. Acute GVHD can be severe and if severe, potentially fatal to the
      transplant recipient. Acute GVHD usually happens within the first several months after
      transplant.

      The goal of this research is to develop a safer and more effective treatment for acute GVHD,
      and particularly for acute GVHD that affects the gastrointestinal (or GI) tract, with the
      ultimate goal being safer and more effective transplant therapies for blood cancers such as
      leukemia, lymphoma, and multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  New onset high risk acute GVHD (Ann Arbor score 2 or3 as defined in Appendix C of the
             protocol) following allogeneic bone marrow transplantation. 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 ≤2 mg/kg/day (or IV methylprednisolone). Topical skin steroid treatment,
             non-absorbable oral steroid treatment for 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.

          -  Age 18 years or older.

          -  Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert
             syndrome or aGVHD within 3 days of enrollment.

          -  ALT/SGPT and AST/SGOT 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.

          -  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 systemic steroid treatment for acute GVHD are not permitted to
             participate.

        Exclusion Criteria:

          -  Progressive or relapsed malignancy since BMT

          -  Uncontrolled active infection

          -  Patients with chronic GVHD only. Patient with overlap syndrome are eligible.

          -  History 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-Investigator