Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced myeloid malignancies

Gautam Borthakur, Michael G. Rosenblum, Moshe Talpaz, Naval Daver, Farhad Ravandi, Stefan Faderl, Emil J. Freireich, Tapan Kadia, Guillermo Garcia-Manero, Hagop Kantarjian, Jorge E. Cortes

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44 Scopus citations

Abstract

We conducted a phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with relapsed, refractory myeloid leukemias. Twenty-eight patients received the construct intravenously at four dose levels (12, 18, 28 and 40 mg/m2 per course) in a "3+3" study design. The dose-limiting toxicity was infusion-related allergic reaction including hypoxia and hypotension. The 28 mg/m2 total dose was considered the maximally tolerated dose. Four patients developed a reduction in peripheral blood blasts of at least 50%. Three patients treated with the 10, 12 and 28 mg/m2 doses showed a 38-50% reduction in bone marrow blasts. There was normalization of platelets in one patient treated with 40 mg/m2. Pharmacokinetic analysis demonstrated that the highest blood levels achieved were 200-300 ng/mL which cleared with a half-life of ~20 hours. Antigenicity was low with one patient at the 12 mg/m2 dose and one patient at the 18 mg/m2 dose (2/23, <10%) developing antibodies to the recombinant gelonin component after 28 days. We concluded that HUM-195/rGel can be safely administered in a multi-dose cycle to patients with advanced myeloid malignancies and warrants further investigation.

Original languageEnglish (US)
Pages (from-to)217-221
Number of pages5
JournalHaematologica
Volume98
Issue number2
DOIs
StatePublished - Feb 1 2013

ASJC Scopus subject areas

  • Hematology

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    Borthakur, G., Rosenblum, M. G., Talpaz, M., Daver, N., Ravandi, F., Faderl, S., Freireich, E. J., Kadia, T., Garcia-Manero, G., Kantarjian, H., & Cortes, J. E. (2013). Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced myeloid malignancies. Haematologica, 98(2), 217-221. https://doi.org/10.3324/haematol.2012.071092