Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease

Anas Younes, Barbara Pro, Michael Robertson, Ian W. Flinn, Jorge E. Romaguera, Fredrick Hagemeister, Nam H. Dang, Paolo Fiumara, Evelyne M. Loyer, Fernando F. Cabanillas, Peter W. McLaughlin, Maria Alma Rodriguez, Felipe Samaniego

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Abstract

Purpose: The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Experimental Design: Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation. Results: All patients were assessable for toxicity, and 39 of 42 (93%) patients were assessable for response. Six of 29 (21%) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/μl to 576/μl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37% of the patients. Conclusions: The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.

Original languageEnglish
Pages (from-to)5432-5438
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number16
DOIs
StatePublished - Aug 15 2004

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Phase II Clinical Trials
Interleukin-12
Hodgkin Disease
Non-Hodgkin's Lymphoma
Therapeutics
Stem Cell Transplantation
Fibroblast Growth Factor 2

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease. / Younes, Anas; Pro, Barbara; Robertson, Michael; Flinn, Ian W.; Romaguera, Jorge E.; Hagemeister, Fredrick; Dang, Nam H.; Fiumara, Paolo; Loyer, Evelyne M.; Cabanillas, Fernando F.; McLaughlin, Peter W.; Rodriguez, Maria Alma; Samaniego, Felipe.

In: Clinical Cancer Research, Vol. 10, No. 16, 15.08.2004, p. 5432-5438.

Research output: Contribution to journalArticle

Younes, A, Pro, B, Robertson, M, Flinn, IW, Romaguera, JE, Hagemeister, F, Dang, NH, Fiumara, P, Loyer, EM, Cabanillas, FF, McLaughlin, PW, Rodriguez, MA & Samaniego, F 2004, 'Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease', Clinical Cancer Research, vol. 10, no. 16, pp. 5432-5438. https://doi.org/10.1158/1078-0432.CCR-04-0540
Younes, Anas ; Pro, Barbara ; Robertson, Michael ; Flinn, Ian W. ; Romaguera, Jorge E. ; Hagemeister, Fredrick ; Dang, Nam H. ; Fiumara, Paolo ; Loyer, Evelyne M. ; Cabanillas, Fernando F. ; McLaughlin, Peter W. ; Rodriguez, Maria Alma ; Samaniego, Felipe. / Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 16. pp. 5432-5438.
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abstract = "Purpose: The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Experimental Design: Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation. Results: All patients were assessable for toxicity, and 39 of 42 (93{\%}) patients were assessable for response. Six of 29 (21{\%}) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/μl to 576/μl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37{\%} of the patients. Conclusions: The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.",
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AU - Younes, Anas

AU - Pro, Barbara

AU - Robertson, Michael

AU - Flinn, Ian W.

AU - Romaguera, Jorge E.

AU - Hagemeister, Fredrick

AU - Dang, Nam H.

AU - Fiumara, Paolo

AU - Loyer, Evelyne M.

AU - Cabanillas, Fernando F.

AU - McLaughlin, Peter W.

AU - Rodriguez, Maria Alma

AU - Samaniego, Felipe

PY - 2004/8/15

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N2 - Purpose: The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Experimental Design: Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation. Results: All patients were assessable for toxicity, and 39 of 42 (93%) patients were assessable for response. Six of 29 (21%) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/μl to 576/μl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37% of the patients. Conclusions: The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.

AB - Purpose: The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Experimental Design: Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation. Results: All patients were assessable for toxicity, and 39 of 42 (93%) patients were assessable for response. Six of 29 (21%) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/μl to 576/μl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37% of the patients. Conclusions: The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.

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