“Safety and Tolerability Trial of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated-Donor Hematopoietic Stem Cell Transplant” is a safety and tolerability study to determine the pharmacokinetic/pharmacodynamic consequences of introducing abatacept as a component of a multi-agent acute graft-versus-host-disease (aGvHD) prophylaxis regimen. The primary objective is to determine the safety and tolerability of the addition of abatacept for aGvHD prophylaxis in transplants for malignant hematologic diseases using unrelated donor bone marrow or peripheral blood stem cell grafts. The trial completed enrollment, enrolling 10 patients at two centers (Emory University and Children’s Healthcare of Atlanta).
Abstract Abatacept 1
We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P < .01). The ABA patients demonstrated a low rate of aGVHD, despite robust immune reconstitution, with 2 of 10 patients diagnosed with grade II-IV aGVHD before day +100, no deaths from infection, no day +100 TRM, and with 7 of 10 evaluable patients surviving (median follow-up, 16 months). These results suggest that costimulation blockade with abatacept can significantly affect CD4(+) T cell proliferation and activation post-transplantation, and may be an important adjunct to standard immunoprophylaxis for aGVHD in patients undergoing unrelated-donor HCT.
Abatacept Combined With a Calcineurin Inhibitor and Methotrexate for Graft Versus Host Disease Prophylaxis: A Randomized Controlled Trial”, is a multicenter phase II trial for patients with hematologic malignancies undergoing hematopoietic stem cell transplant. The primary objective of the study is to determine whether the addition of abatacept combined with standard immunoprophylaxis will reduce the incidence of severe acute graft-versus-host disease (aGVHD). aGVHD is a common complication of transplant and is associated with significant morbidity and mortality. aGVHD is caused by the T cells from the donor (graft) attacking the patient (host) and causing damage to tissues. Abatacept works by preventing T cells from becoming activated and will, hopefully, prevent the tissue damage from occurring. The Abatacept clinical trial completed enrollment, enrolling 186 patients at 14 centers across the US and Canada.
A Randomized Double-Blind Trial of Abatacept Extended Dosing Versus Abatacept Short-term dosing for Graft Versus Host Disease Prophylaxis: ABA3” is a multi-center, phase II trial for patients receiving transplants from 7 of 8 HLA matched donors. The primary objective of this trial is to determine whether an 8-dose regimen of abatacept will improve the rate of severe acute GVHD-free, severe chronic GVHD-free, relapse-free survival compared to a 4-dose regimen of abatacept after transplant.