title: A phase 1 study evaluating the safety and tolerability of otlertuzumab, an anti-CD37 mono-specific ADAPTIR therapeutic protein in chronic lymphocytic leukemia.
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.
authors.affiliation: Division of Hematology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH;
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Awan
authors.forename: Andres
authors.initials: A
authors.lastname: Forero
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.forename: Delva P
authors.initials: DP
authors.lastname: Deauna-Limayo
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Spurgeon
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Andritsos
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eisenfeld
authors.forename: Jeannette E
authors.initials: JE
authors.lastname: Bannink
authors.forename: Scott C
authors.initials: SC
authors.lastname: Stromatt
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D059470:Tetraspanins / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C059071:CD37 protein, human; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C547387:TRU 016; D059470:Tetraspanins