PHASE-I CLINICAL-TRIAL OF SEROTHERAPY IN PATIENTS WITH ACUTE MYELOID-LEUKEMIA WITH AN IMMUNOGLOBULIN-M MONOCLONAL-ANTIBODY TO CD15

Sixteen patients with acute myeloid leukemia (AML) mere treated with a continuous i.v. infusion of mAb PM-81, an IgM mAb directed against th e cellular differentiation antigen CD15, which is expressed on leukemi a cells of >95% of patients with AML, MAb PM-81, also referred to as M DX-11, is capable of activating human and rabbit complement and lysing CD15-positive AML cells, In this Phase I study, patients were treated with 0.5, 1.0, or 1.5 mg/kg MDX-11 delivered over a 24-h period follo wed by conventional chemotherapy, Transient decreases in circulating b last cells postinfusion (prior to chemotherapy) were observed at all d oses, We were able to show MDX-11 binding to bone marrow blasts in tho se patients who achieved stable serum levels of MDX-11, Serum MDX-11 w as detectable at the 1.0- and 1.5-mg/kg doses, Doses of 0.5 and 1.0 mg /kg were generally well tolerated, with no toxicities greater than gra de II (Eastern Cooperative Oncology Group) reported. However, two of f ive patients receiving the 1.5-mg/kg dose experienced grade IV toxicit ies that resolved with treatment (one of these patients completed the infusion), Common toxicities reported included fever, chills, and hypo tension, Only one patient developed human antimouse antibodies at 4 we eks posttreatment, This study determined that 1.0 mg/kg is a biologica lly effective dose that can be administered safely with little toxicit y. Based on these results, we are pursuing a Phase I/II study of MDX-1 1 infusion following chemotherapy for patients with relapsed AML.