A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia

John C. Byrd, John M. Pagel, Farrukh T. Awan, Andres Forero, Ian W. Flinn, Delva P. Deauna-Limayo, Stephen E. Spurgeon, Leslie A. Andritsos, Ajay K. Gopal, John P. Leonard, Amy J. Eisenfeld, Jeannette E. Bannink, Scott C. Stromatt, Richard R. Furman

Research output: Contribution to journalArticle

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Abstract

Otlertuzumab is a novel humanized anti-CD37 protein therapeutic. This study evaluated the safety of otlertuzumab administered intravenously to patients with chronic lymphocytic leukemia (CLL). Otlertuzumab was administered weekly for up to 8 weeks followed by 1 dose per month for 4 months ranging from 0.03 to 20 mg/kg in the dose-escalation phase and 10 to 30 mg/kg in the dose-expansion phase. Responses were determined by using the 1996 National Cancer Institute (NCI-96) and 2008 International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) criteria. Fifty-seven patients were treated in the dose-escalation phase and 26 in the dose-expansion phase. A maximum-tolerated dose was not identified. Response occurred in 19 (23%) of 83 treated patients by NCI-96 criteria. All responses were partial and occurred more commonly in patients with symptomatic untreated CLL (6/7) or 1 to 2 prior therapies (12/28) vs 3 or more therapies (1/48). Twenty percent (12/61) with serial computed tomography scan assessment had a response per IWCLL criteria. The most frequent adverse events were infusion reactions, fatigue, nausea, and diarrhea and were not dose related. Otlertuzumab was well tolerated, and modest clinical activity was observed. Otlertuzumab warrants further evaluation in combination with other agents for the treatment of CLL. This trial was registered at www.clinicaltrials.gov as #NCT00614042.

Original languageEnglish (US)
Pages (from-to)1302-1308
Number of pages7
JournalBlood
Volume123
Issue number9
DOIs
StatePublished - Feb 27 2014
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Safety
Proteins
Therapeutics
Education
Maximum Tolerated Dose
National Cancer Institute (U.S.)
Nausea
Fatigue
Tomography
Diarrhea
TRU 016
Fatigue of materials

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia. / Byrd, John C.; Pagel, John M.; Awan, Farrukh T.; Forero, Andres; Flinn, Ian W.; Deauna-Limayo, Delva P.; Spurgeon, Stephen E.; Andritsos, Leslie A.; Gopal, Ajay K.; Leonard, John P.; Eisenfeld, Amy J.; Bannink, Jeannette E.; Stromatt, Scott C.; Furman, Richard R.

In: Blood, Vol. 123, No. 9, 27.02.2014, p. 1302-1308.

Research output: Contribution to journalArticle

Byrd, JC, Pagel, JM, Awan, FT, Forero, A, Flinn, IW, Deauna-Limayo, DP, Spurgeon, SE, Andritsos, LA, Gopal, AK, Leonard, JP, Eisenfeld, AJ, Bannink, JE, Stromatt, SC & Furman, RR 2014, 'A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia', Blood, vol. 123, no. 9, pp. 1302-1308. https://doi.org/10.1182/blood-2013-07-512137
Byrd, John C. ; Pagel, John M. ; Awan, Farrukh T. ; Forero, Andres ; Flinn, Ian W. ; Deauna-Limayo, Delva P. ; Spurgeon, Stephen E. ; Andritsos, Leslie A. ; Gopal, Ajay K. ; Leonard, John P. ; Eisenfeld, Amy J. ; Bannink, Jeannette E. ; Stromatt, Scott C. ; Furman, Richard R. / A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia. In: Blood. 2014 ; Vol. 123, No. 9. pp. 1302-1308.
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abstract = "Otlertuzumab is a novel humanized anti-CD37 protein therapeutic. This study evaluated the safety of otlertuzumab administered intravenously to patients with chronic lymphocytic leukemia (CLL). Otlertuzumab was administered weekly for up to 8 weeks followed by 1 dose per month for 4 months ranging from 0.03 to 20 mg/kg in the dose-escalation phase and 10 to 30 mg/kg in the dose-expansion phase. Responses were determined by using the 1996 National Cancer Institute (NCI-96) and 2008 International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) criteria. Fifty-seven patients were treated in the dose-escalation phase and 26 in the dose-expansion phase. A maximum-tolerated dose was not identified. Response occurred in 19 (23{\%}) of 83 treated patients by NCI-96 criteria. All responses were partial and occurred more commonly in patients with symptomatic untreated CLL (6/7) or 1 to 2 prior therapies (12/28) vs 3 or more therapies (1/48). Twenty percent (12/61) with serial computed tomography scan assessment had a response per IWCLL criteria. The most frequent adverse events were infusion reactions, fatigue, nausea, and diarrhea and were not dose related. Otlertuzumab was well tolerated, and modest clinical activity was observed. Otlertuzumab warrants further evaluation in combination with other agents for the treatment of CLL. This trial was registered at www.clinicaltrials.gov as #NCT00614042.",
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AU - Awan, Farrukh T.

AU - Forero, Andres

AU - Flinn, Ian W.

AU - Deauna-Limayo, Delva P.

AU - Spurgeon, Stephen E.

AU - Andritsos, Leslie A.

AU - Gopal, Ajay K.

AU - Leonard, John P.

AU - Eisenfeld, Amy J.

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