Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients

Stephen Maxted Ansell, Susan M. Geyer, Matthew J. Maurer, Paul J. Kurtin, Ivana Micallef, Philip Stella, Paul Etzell, Anne J Novak, Charles Erlichman, Thomas Elmer Witzig

Research output: Contribution to journalArticle

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Abstract

Purpose: 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). Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)6056-6063
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number20 PART 1
DOIs
StatePublished - Oct 15 2006

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Interleukin-12
Non-Hodgkin's Lymphoma
B-Cell Lymphoma
Rituximab
Biopsy
Therapeutics
Natural Killer Cells
Blood Cells
B-Lymphocytes
Research Design
Lymph Nodes
Apoptosis
T-Lymphocytes
Gene Expression
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients. / Ansell, Stephen Maxted; Geyer, Susan M.; Maurer, Matthew J.; Kurtin, Paul J.; Micallef, Ivana; Stella, Philip; Etzell, Paul; Novak, Anne J; Erlichman, Charles; Witzig, Thomas Elmer.

In: Clinical Cancer Research, Vol. 12, No. 20 PART 1, 15.10.2006, p. 6056-6063.

Research output: Contribution to journalArticle

Ansell, Stephen Maxted ; Geyer, Susan M. ; Maurer, Matthew J. ; Kurtin, Paul J. ; Micallef, Ivana ; Stella, Philip ; Etzell, Paul ; Novak, Anne J ; Erlichman, Charles ; Witzig, Thomas Elmer. / Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 20 PART 1. pp. 6056-6063.
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T1 - Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients

AU - Ansell, Stephen Maxted

AU - Geyer, Susan M.

AU - Maurer, Matthew J.

AU - Kurtin, Paul J.

AU - Micallef, Ivana

AU - Stella, Philip

AU - Etzell, Paul

AU - Novak, Anne J

AU - Erlichman, Charles

AU - Witzig, Thomas Elmer

PY - 2006/10/15

Y1 - 2006/10/15

N2 - Purpose: 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). Experimental Design: 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.

AB - Purpose: 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). Experimental Design: 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.

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