A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of OTI-010 in Subjects Who Receive HLA-Identical Sibling Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

OBJECTIVES:

• Compare the safety and efficacy of OTI-010 vs placebo as graft-versus-host disease prophylaxis in patients with hematologic malignancies undergoing HLA-identical sibling matched peripheral blood stem cell transplantation.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18 to 34 vs 35 to 55) and donor/recipient gender (female donor/male recipient vs female donor/female recipient vs male donor/female recipient vs male donor/male recipient).

• Conditioning regimen: Patients receive cyclophosphamide IV once daily on days -5 and -4 and undergo total body irradiation twice daily on days -3 to -1 OR busulfan IV over 2 hours every 6 hours on days -7 to -4 and cyclophosphamide IV once daily on days -3 and -2.

• Graft-versus-host disease prophylaxis: Patients receive methotrexate IV on days 1, 3, 6, and 11. Patients also receive cyclosporine orally or IV (over 1-4 hours) twice daily beginning on day -1 and continuing for at least 6 months followed by a taper until 1 year after transplantation.

• OTI-010 therapy: Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive placebo IV 4 hours before peripheral blood stem cell transplantation (PBSCT) on day 0.

• Arm II: Patients receive OTI-010 IV 4 hours before PBSCT on day 0.

• Arm III: Patients receive a higher dose of OTI-010 IV 4 hours before PBSCT on day 0.

• Allogeneic stem cell transplantation: Patients undergo allogeneic PBSCT on day 0.