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

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...

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Bibliographic Details
Published in:Leukemia & lymphoma 2012-02, Vol.53 (2), p.211-217
Main Authors: Zent, Clive S., Smith, Brian J., Ballas, Zuhair K., Wooldridge, James E., Link, Brian K., Call, Timothy G., Shanafelt, Tait D., Bowen, Deborah A., Kay, Neil E., Witzig, Thomas E., Weiner, George J.
Format: Article
Language:English
Subjects:
Adult
Aged
Chronic lymphocytic leukemia
CLL
CpG 2006
CpG oligonucleotide 7909
Female
Follow-Up Studies
Humans
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - genetics
Oligodeoxyribonucleotides - therapeutic use
PF-03512676
Prognosis
Salvage Therapy
TLR9
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Summary: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.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2011.608451