Phase I Trial of Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox (CAT-8015 or HA22) in Patients With Hairy Cell Leukemia

Purpose To conduct a phase I dose-escalation trial assessing safety and response of recombinant immunotoxin moxetumomab pasudotox (CAT-8015, HA22) in chemotherapy-resistant hairy cell leukemia (HCL). Patients and Methods Eligible patients had relapsed/refractory HCL after >= two prior therapies and required treatment because of abnormal blood counts. Patients received moxetumomab pasudotox 5 to 50 mu g/kg every other day for three doses (QOD x3), with up to 16 cycles repeating at >= 4-week intervals if patients did not experience disease progression or develop neutralizing antibodies. Results Twenty-eight patients were enrolled, including three patients each at 5, 10, 20, and 30 mu g/kg, four patients at 40 mu g/kg, and 12 patients at 50 mu g/kg QOD x3 for one to 16 cycles each (median, four cycles). Dose-limiting toxicity was not observed. Two patients had transient laboratory abnormalities consistent with grade 2 hemolytic uremic syndrome with peak creatinine of 1.53 to 1.66 mg/dL and platelet nadir of 106,000 to 120,000/mu L. Drug-related toxicities in 25% to 64% of the 28 patients included (in decreasing frequency) grade 1 to 2 hypoalbuminemia, aminotransferase elevations, edema, headache, hypotension, nausea, and fatigue. Of 26 patients evaluable for immunogenicity, 10 patients (38%) made antibodies neutralizing more than 75% of the cytotoxicity of 1,000 ng/mL of immunotoxin, but this immunogenicity was rare (5%) after cycle 1. The overall response rate was 86%, with responses observed at all dose levels, and 13 patients (46%) achieved complete remission (CR). Only 1 CR lasted less than 1 year, with the median disease-free survival time not yet reached at 26 months. Conclusion Moxetumomab pasudotox at doses up to 50 mu g/kg QOD x3 has activity in relapsed/refractory HCL and has a safety profile that supports further clinical development for treatment of this disease. J Clin Oncol 30:1822-1828. (c) 2012 by American Society of Clinical Oncology