Clinical Trial: Safety and Tolerability Trial of Abatacept-based Immunosuppression for Prevention of Acute Graft Versus Host Disease (aGVHD) During Transplant

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Safety and Tolerability Trial of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor Hematopoietic Stem Cell Transplant

Brief Summary: The primary objective of the study is to determine the safety and tolerability when adding abatacept to acute Graft versus Host Disease in transplants for malignant diseases using unrelated donor bone marrow or peripheral blood stem cell grafts.

Detailed Summary:

Acute Graft versus Host Disease (aGvHD) is the most deadly complication facing children who have allogeneic hematopoietic stem cell transplant (HSCT). aGvHD occurs, in large part, because the T cells in the bone marrow graft do not "accept" the presence of the transplant recipient's cells, and mount a severe, debilitating, and often deadly attack against the recipient, striking the skin, the liver, and the gastrointestinal track, most prominently. For patients receiving bone marrow from an unrelated donor, the rate of aGvHD can reach as high as 80%, with up to half of patients dying from this complication. These serious outcomes occur despite our best efforts at aGvHD prevention. Given the lack of success in preventing aGvHD with current therapies, novel therapies to prevent this disease are desperately needed.

In this study, we plan to test a novel drug to prevent aGvHD. This drug, known as abatacept, specifically blocks the activation pathway critical to T cell function known as "T cell costimulation." In particular, it blocks the CD28-mediated costimulation pathway that is critical for optimal T cell activation and proliferation. My research group has done extensive pre-clinical work with this compound. Our work has demonstrated its efficacy in inducing immune tolerance after transplantation in both mouse models and primate models. In addition, patient trials have demonstrated that blocking CD28-directed T cell costimulation can prevent T cell-mediated diseases, including rheumatoid arthritis and psoriasis, and can improve solid organ transplant acceptance. Abatacept is currently FDA approved for use in rheumatoid arthritis. Given this drug's safety and efficacy profile, we have been granted an IND-exemption from the FDA for the inclusion of abatacept in a GvHD-prevention strategy.

This is a safety a
Sponsor: Emory University

Current Primary Outcome: Safety and tolerability of the addition of abatacept to aGvHD prophylaxis in transplants for malignant hematologic disease using unrelated donor bone marrow or peripheral blood stem cell grafts. [ Time Frame: 3 years after transplant ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence and severity of aGvHD in patients receiving the abatacept-based protocol. [ Time Frame: 3 years after transplant ]
  • Immune phenotype of donor cells in patients receiving abatacept. [ Time Frame: 3 years after transplant ]
  • The ability of donor T-cells in patients receiving abatacept to respond to both polyclonal and recipient-specific immune stimulation. [ Time Frame: 3 years after transplant ]


Original Secondary Outcome: Same as current

Information By: Emory University

Dates:
Date Received: November 11, 2009
Date Started: November 2009
Date Completion: December 2013
Last Updated: November 12, 2009
Last Verified: November 2009