title: Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
abstract: BACKGROUND
  This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.
  
  
  METHODS
  Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.
  
  
  RESULTS
  Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.
  
  
  CONCLUSIONS
  Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.
authors: Department of Medicine, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA 94305, USA. mliedtke@stanford.edu
authors: Michaela
authors: M
authors: Liedtke
authors: Clare J
authors: CJ
authors: Twist
authors: Bruno C
authors: BC
authors: Medeiros
authors: Jason R
authors: JR
authors: Gotlib
authors: Caroline
authors: C
authors: Berube
authors: Marcia M
authors: MM
authors: Bieber
authors: Neelima M
authors: NM
authors: Bhat
authors: Nelson N
authors: NN
authors: Teng
authors: Steven E
authors: SE
authors: Coutre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000936:Antigen-Antibody Complex; D000970:Antineoplastic Agents; D014750:Vincristine