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

Research output: Contribution to journalArticle

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
Externally publishedYes

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Immunotoxins
Neoplasms
Myeloid Leukemia
Maximum Tolerated Dose
monoclonal antibody M195
Gelonium multiflorum GEL protein
Hypotension
Half-Life
Hypersensitivity
Blood Platelets
Pharmacokinetics
Bone Marrow
Antibodies

ASJC Scopus subject areas

  • Hematology

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

In: Haematologica, Vol. 98, No. 2, 01.02.2013, p. 217-221.

Research output: Contribution to journalArticle

Borthakur, G, Rosenblum, MG, Talpaz, M, Daver, N, Ravandi, F, Faderl, S, Freireich, EJ, Kadia, T, Garcia-Manero, G, Kantarjian, H & Cortes, JE 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, vol. 98, no. 2, pp. 217-221. https://doi.org/10.3324/haematol.2012.071092
Borthakur, Gautam ; Rosenblum, Michael G. ; Talpaz, Moshe ; Daver, Naval ; Ravandi, Farhad ; Faderl, Stefan ; Freireich, Emil J. ; Kadia, Tapan ; Garcia-Manero, Guillermo ; Kantarjian, Hagop ; Cortes, Jorge E. / 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. In: Haematologica. 2013 ; Vol. 98, No. 2. pp. 217-221.
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