title: Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients.
abstract: OBJECTIVE
  Rituximab is a chimeric antibody that induces B-cell apoptosis and recruits immune effector cells to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic responses by T cells and natural killer cells. This phase II study was done to determine the efficacy and toxicity of IL-12 in combination with rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Fifty-eight patients with histologically confirmed relapsed B-cell NHL were randomized to receive concurrent treatment with rituximab and IL-12 (arm A) or rituximab with subsequent treatment with IL-12 after documented nonresponse or progression after rituximab (arm B). Treatment consisted of 375 mg/m2 rituximab on days 1, 8, 15, and 22 and 300 ng/kg IL-12 given s.c. twice weekly starting on day 2 for arm A or upon progression for arm B.
  
  
  RESULTS
  The overall response rate was 37% (11 of 30) in arm A and 52% (13 of 25) in arm B. All of the responses seen in arm B occurred while patients received rituximab, and no responses occurred during treatment with subsequent IL-12. The median duration of response was 16 months for arm A and 12 months for arm B. Biopsy specimens were serially obtained in a subset of patients and showed that changes in gene expression were different when cells from the peripheral blood were compared with cells from lymph node biopsies.
  
  
  CONCLUSIONS
  The concomitant use of IL-12 and rituximab had modest disease activity in patients with B-cell NHL, but the sequential administration of IL-12 after rituximab did not result in additional clinical responses.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota and North Central Cancer Treatment Group, Rochester, Minnesota 55905, USA. ansell.stephen@mayo.edu
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Geyer
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: Ivana N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: Philip
authors.initials: P
authors.lastname: Stella
authors.forename: Paul
authors.initials: P
authors.lastname: Etzell
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use* / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018664:Interleukin-12 / Q000627:therapeutic use* / Q000633:toxicity; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D018664:Interleukin-12; D000069283:Rituximab