Phase i clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia

Clive S. Zent, Brian J. Smith, Zuhair K. Ballas, James E. Wooldridge, Brian K. Link, Timothy G. Call, Tait D. Shanafelt, Deborah A. Bowen, Neil E. Kay, Thomas E. Witzig, George J. Weiner

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

CpG oligonucleotide 7909 (CpG 7909, PF-03512676), a synthetic 24mer single stranded agonist of TLR9 expressed by B cells and plasmacytoid dendritic cells, is immunomodulatory and can cause activation-induced death of chronic lymphocytic leukemia (CLL) cells. We report a phase I study of CpG 7909 in 41 patients with early relapsed CLL. A single intravenous dose of CpG 7909 was well tolerated with no clinical effects and no significant toxicity up to 1.05 mg/kg. Single dose subcutaneous CpG 7909 had a maximum tolerated dose (MTD) of 0.45 mg/kg with dose limiting toxicity of myalgia and constitutional effects. Multiple weekly subcutaneous doses at the MTD were well tolerated. CpG 7909 administration induced immunologic changes in CLL and non-malignant cells that were dose and route dependent. We conclude that multidose therapy with subcutaneous CpG 7909 (0.45 mg/kg) could be used in future phase II combination clinical trials for CLL.

Original languageEnglish (US)
Pages (from-to)211-217
Number of pages7
JournalLeukemia and Lymphoma
Volume53
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • CLL
  • Chronic lymphocytic leukemia
  • CpG 2006
  • CpG oligonucleotide 7909
  • PF-03512676
  • TLR9

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Zent, C. S., Smith, B. J., Ballas, Z. K., Wooldridge, J. E., Link, B. K., Call, T. G., Shanafelt, T. D., Bowen, D. A., Kay, N. E., Witzig, T. E., & Weiner, G. J. (2012). Phase i clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia. Leukemia and Lymphoma, 53(2), 211-217. https://doi.org/10.3109/10428194.2011.608451