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

• 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
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2011.608451

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.