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 language | English (US) |
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Pages (from-to) | 211-217 |
Number of pages | 7 |
Journal | Leukemia and Lymphoma |
Volume | 53 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2012 |
Keywords
- CLL
- Chronic lymphocytic leukemia
- CpG 2006
- CpG oligonucleotide 7909
- PF-03512676
- TLR9
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research