Treatment for Acute Graft-Versus-Host Disease (BMT CTN 0302)
Condition: Graft vs Host Disease; Immune System Disorders
MeSH terms: Graft vs Host Disease; Immune System Diseases
Intervention: Etanercept; Mycophenolate Mofetil; Denileukin Diftitox; Pentostatin
Intervention description: Etanercept [25 mg subcutaneously twice weekly for up to 4 weeks; discontinue if in complete response by 4 weeks].; Mycophenolate mofetil (MMF) [20 mg/kg (maximum 1 gm) orally or intravenously twice daily; continue through prednisone taper, then taper MMF over 4 weeks].; Denileukin Diftitox (ONTAK®) [9 mcg/kg intravenously Days 1, 3, 5, 15, 17, 19].; Pentostatin [1.5 mg/m2 daily for 3 days; Days 1-3 and repeat Days 15-17
Intervention MeSH terms: Mycophenolic Acid; Etanercept; Pentostatin; Denileukin diftitox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 180.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Acute Graft vs Host Disease; GVHD

Summary:

      The study is a randomized Phase II, four arm treatment trial. The primary purpose of the
      study is to define new agents with promising activity against acute graft-versus-host disease
      (GVHD) suitable for testing against corticosteroids alone in a subsequent Phase III trial.
    

Eligibility criteria:

        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

          -  Absolute neutrophil count (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