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

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.

• Authors: Stephen M Ansell, Susan M Geyer, Matthew J Maurer, Paul J Kurtin, Ivana N M Micallef, Philip Stella, Paul Etzell, Anne J Novak, Charles Erlichman, Thomas E Witzig
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 20 Pt 1 Pg. 6056-63 (Oct 15 2006) ISSN: 1078-0432 [Print] United States
• PMID: 17062681 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• RNA, Neoplasm
• Interleukin-12
• Rituximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (therapeutic use, toxicity)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents (therapeutic use, toxicity)
• Drug Administration Schedule
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interleukin-12 (therapeutic use, toxicity)
• Lymphoma, B-Cell (drug therapy, genetics, immunology)
• Lymphoma, Non-Hodgkin (drug therapy, genetics, immunology)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Patient Selection
• RNA, Neoplasm (genetics, isolation & purification)
• Rituximab
• T-Lymphocytes (immunology)