GVH 022P: Study Using Anti Tumor Necrosis Factor Antibody (Infliximab) for Treatment of Acute Graft Versus Host Disease
Status:
Completed
Trial end date:
2006-10-01
Target enrollment:
Participant gender:
Summary
Acute graft versus host disease (GVHD) remains one of the most significant and potentially
lethal complications of allogeneic bone marrow transplantation. Depending upon the type of
transplant, the incidence of acute GVHD varies between 20 - 50% in related donor transplants,
or as high as 70 - 90% in unrelated donor transplants. Acute GVHD affects the skin, liver and
gastrointestinal (GI) tract and usually occurs within 20 - 40 days of the bone marrow
infusion.
Steroids are the standard initial treatment of acute GVHD, with approximately 50% of the
patients either free of disease or requiring no further therapy. In the remaining patients,
the GVHD either does not respond or it comes back during the tapering of steroids. These
patients have a much worse prognosis with a mortality rate greater than 70%. Studies using
additional agents such as antithymocyte globulin (ATG), monoclonal antibodies, and
anti-lymphocyte globulin showed no improvement over the use of steroids alone. This leads the
investigators to look for new immunosuppressive agents that can reduce the risk and severity
of acute GVHD.
The major purpose of this study is to evaluate the way the body uses and absorbs (the
pharmacokinetic profile) a drug called anti tumor necrosis factor antibody (infliximab) for
the treatment of acute GVHD. Infliximab is currently indicated for the treatment of
immunologic-based diseases (rheumatoid arthritis, moderately to severely active Crohn's
disease, and fistulizing Crohn's disease), assuming patients have had inadequate responses to
conventional therapy. It is not approved for the treatment of GVHD.
This is a Phase I pharmacokinetic study that is coordinated by the Pediatric Blood and Marrow
Transplant Consortium (PBMTC). The study will be conducted in the Blood and Marrow
Transplantation (BMT) program at Children's Healthcare of Atlanta - Egleston, Emory
University Department of Pediatrics. The goal is to enroll 1 - 2 patients on this study;
accrual will be via the BMT program. Eligible patients must be less than 18 years of age.
Patients with newly diagnosed acute GVHD will be able to participate in the study. Patients
will receive a single dose of infliximab in the clinic. Since this is a Phase I study, the
patients will have blood samples drawn to measure the pharmacokinetics of the drug. A total
of 16 blood samples will be drawn over 84 days. The samples will be labeled with a code,
processed, frozen, and then sent in a batch to the PBMTC designated laboratory for testing.
Patients will continue on any drugs they were getting for the prevention of GVHD. Additional
doses of infliximab may be given. This decision will be based on the results of the blood
testing.