期刊
LEUKEMIA & LYMPHOMA
卷 53, 期 2, 页码 211-217出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10428194.2011.608451
关键词
Chronic lymphocytic leukemia; CLL; CpG oligonucleotide 7909; PF-03512676; CpG 2006; TLR9
资金
- University of Iowa/Mayo Clinic Lymphoma SPORE [CA097274]
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.
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