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

Overview

MeSH

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Protein Engineering
  • Tetraspanins
  • Treatment Outcome

MeSH Major

  • Antineoplastic Agents
  • Immunoglobulin G
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Recombinant Fusion Proteins

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.

publication date

  • February 27, 2014

has subject area

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Female
  • Humans
  • Immunoglobulin G
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Protein Engineering
  • Recombinant Fusion Proteins
  • Tetraspanins
  • Treatment Outcome

Research

keywords

  • Clinical Trial, Phase I
  • Journal Article
  • Multicenter Study

Identity

Language

  • eng

PubMed Central ID

  • PMC3938145

Digital Object Identifier (DOI)

  • 10.1182/blood-2013-07-512137

PubMed ID

  • 24381226

Additional Document Info

start page

  • 1302

end page

  • 1308

volume

  • 123

number

  • 9