title: A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma.
abstract: BACKGROUND
  Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin's lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety, pharmacokinetics, and efficacy were evaluated.
  
  
  METHODS
  Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractory patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m(2)) and rituximab (375 mg/m(2)). International Workshop Response Criteria (IWRC) were used to evaluate response.
  
  
  RESULTS
  Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics.
  
  
  CONCLUSIONS
  These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated.
authors.affiliation: Division of Hematology/Oncology, Weill Medical College of Cornell University and NewYork-Presbyterian Hospital, New York, NY 10021, USA. jpleonar@med.cornell.edu
authors.forename: J P
authors.initials: JP
authors.lastname: Leonard
authors.forename: J W
authors.initials: JW
authors.lastname: Friedberg
authors.forename: A
authors.initials: A
authors.lastname: Younes
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: L I
authors.initials: LI
authors.lastname: Gordon
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Czuczman
authors.forename: T
authors.initials: T
authors.lastname: Miller
authors.forename: P
authors.initials: P
authors.lastname: Stiff
authors.forename: B D
authors.initials: BD
authors.lastname: Cheson
authors.forename: A
authors.initials: A
authors.lastname: Forero-Torres
authors.forename: N
authors.initials: N
authors.lastname: Chieffo
authors.forename: B
authors.initials: B
authors.lastname: McKinney
authors.forename: D
authors.initials: D
authors.lastname: Finucane
authors.forename: A
authors.initials: A
authors.lastname: Molina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; C437823:galiximab