title: Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia.
abstract: OBJECTIVE
  Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML).
  
  
  METHODS
  Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m(2), etoposide 80 mg/m(2), and cytarabine 1 g/m(2) daily for 6 days (MEC) in combination with lintuzumab 12 mg/m(2), or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity.
  
  
  RESULTS
  A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion-related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy.
  
  
  CONCLUSIONS
  The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.
authors.affiliation: Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021, USA. ejf2001@med.cornell.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
authors.forename: Joseph
authors.initials: J
authors.lastname: Brandwein
authors.forename: Richard
authors.initials: R
authors.lastname: Stone
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.forename: Joseph
authors.initials: J
authors.lastname: Moore
authors.forename: Julie
authors.initials: J
authors.lastname: O'Connor
authors.forename: Nancy
authors.initials: N
authors.lastname: Wedel
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
authors.forename: Carole
authors.initials: C
authors.lastname: Miller
authors.forename: Raj
authors.initials: R
authors.lastname: Chopra
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Jurcic
authors.forename: Randy
authors.initials: R
authors.lastname: Brown
authors.forename: W Christopher
authors.initials: WC
authors.lastname: Ehmann
authors.forename: Philip
authors.initials: P
authors.lastname: Schulman
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Frankel
authors.forename: Daniel
authors.initials: D
authors.lastname: De Angelo
authors.forename: David
authors.initials: D
authors.lastname: Scheinberg
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; C477390:lintuzumab