Phase II Trial of Infliximab for the Prevention of Acute Graft-versus-Host Disease Following Allogenic Hematopoietic Stem Cell Transplantation
Rationale: Acute graft host disease (GvHD) remains a barrier to successful hematopoietic
stem cell transplantation (HCT) used for the treatment of cancers in some patients. GvHD can
result from a lack of compatibility between the donor and recipient. Research suggests
another primary cause of GvHD comes from cytokines, or a substance produced by cells of the
immune system that affect the immune response in both positive and negative ways. Infliximab
is an antibody that directly targets the cytokine associated with GvHD. This study is
building upon previous research to assess infliximab's ability to prevent GvHD after HCT.
Purpose: This study is evaluating the efficacy of infliximab in reducing the incidence of
GvHD after HCT. The safety of this approach, along with changes to specific cytokines from
this treatment, will also be measured.
Treatment: Patients in this study will receive infliximab through intravenous infusion.
Infliximab will be administered in six doses, including one day before chemotherapy or
radiotherapy, after the stem cell infusion, and then on days 7, 14, 28 and 42. Standard
post-transplant treatments of cyclosporine (Neoral) and methotrexate (Methotrexate) will
also be given through intravenous infusion. Cyclosporine will be given on day 1, and the
subsequent schedule will be determined on an individual basis. Methotrexate will be
administered on days 1, 3, 6, and 11. Several tests and exams will be given throughout the
study to closely monitor patients.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Evaluate efficacy of infliximab in reducing incidence of grade II-IV acute GvHD by day +100 post transplant in patients undergoing allogenic HCT and receiving standard cyclosporine and short course methotrexate GvHD prophylaxis.
For matched related donor transplants, we will test the null hypothesis H0: p ≥0.40 versus the alternative H1: p≤0.20, where p is the probability of grade II-IV acute GvHD by day +100. For matched unrelated donor transplants, we will test the null hypothesis H0: p≥0.70 versus the alternative H1: p≤0.50, where p is the probability of grade II-IV acute GvHD by day +100.
Craig Hofmeister, MD
Ohio State University
United States: Institutional Review Board
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