title: Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  This single-center, dose-escalation study examines the safety, efficacy, and pharmacokinetics of epratuzumab (anti-CD22 humanized monoclonal antibody) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Patients had indolent NHL and recurrent disease after at least one chemotherapy regimen. Epratuzumab was administered intravenously at 120 to 1,000 mg/m2 over 30 to 60 minutes weekly for four treatments.
  
  
  RESULTS
  Fifty-five patients received epratuzumab and were assessable for safety; 51 patients were assessable for response. Patients were heavily pretreated (50% had at least four prior regimens) and 49% had bulky disease (> or = 5 cm). Epratuzumab was well tolerated, with no dose-limiting toxicity. Circulating B cells transiently decreased without significant effects on T cells or immunoglobulin levels. More than 95% of infusions were completed in approximately 1 hour. Mean serum half-life was 23 days. Across all dose levels and histologies, nine patients (18%; 95% confidence interval, 8% to 31%) achieved objective response, including three complete responses (CRs). All responses were in patients with follicular NHL: 24% of these patients responded, including 43% in the 360 mg/m2 dose group and 27% in the 480 mg/m2 dose group. No responses were observed in other indolent histologies. Median duration of objective response was 79.3 weeks (range, 11.1 to 143.3 weeks), with median time to progression for responders of 86.6 weeks by Kaplan-Meier estimate.
  
  
  CONCLUSIONS
  Epratuzumab was well tolerated at up to 1,000 mg/m2/wk (for 4 weeks) and had clinical activity. One third of responding patients achieved CR. A 43% objective response rate in follicular NHL patients treated at 360 mg/m2/wk indicates that this dose should be explored in additional studies.
authors.affiliation: Center for Lymphoma and Myeloma, Division of Hematology and Oncology, Weill Medical College of Cornell University and New York Presbyterian Hospital, 520 East 70th Street, New York, NY 10021, USA. jpleonar@med.cornell.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Ketas
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Scott
authors.initials: S
authors.lastname: Ely
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hansen
authors.forename: Heather
authors.initials: H
authors.lastname: Ziccardi
authors.forename: Michael
authors.initials: M
authors.lastname: Eschenberg
authors.forename: Urte
authors.initials: U
authors.lastname: Gayko
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cesano
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules; D005260:Female; D006207:Half-Life; D006801:Humans; D037102:Lectins / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D051918:Sialic Acid Binding Ig-like Lectin 2
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab