Phase I clinical trial of the anti-CD33 immunotoxin HuM195/rgel in patients (pts) with advanced myeloid malignancies.

6549 Background: HuM195 is a humanized version of the mouse M195 anti CD-33 monoclonal antibody. CD33 is heavily expressed on the surface of myeloid leukemia cells. The anti-CD33 immunotoxin HuM195/rGel combines HuM195 with recombinant gelonin, a RNA glycosidase that inhibits protein synthesis. Methods: The primary objective of this study was to determine the safety and toxicity of HuM195/rGel in pts with refractory or relapsed leukemia. Pts age ≥ 18 years with relapsed or refractory AML, RAEB-t, RAEB, CMML or CML-AP/BP and CD 33 expression ≥ 80% by flow cytometry, were eligible. Pts received doses of 2.5 to 10 mg/m2 using a standard 3 + 3 design. Therapy was administered over 2 one-hour infusions per week for 2 weeks followed by a 2 week period of observation. Pts taken off study before 28 days for reasons other than toxicity were replaced for MTD calculations. Results: 28 patients were enrolled: 23 AML, 4 MDS, and 1 CMML. Median age was 68 years, median number of prior therapies was 2, median peripheral...