Journal article
Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia
Leukemia & lymphoma, Vol.53(2), pp.211-217
02/01/2012
DOI: 10.3109/10428194.2011.608451
PMCID: PMC3438221
PMID: 21812536
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.
Details
- Title: Subtitle
- Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia
- Creators
- Clive S Zent - Division of Hematology, Mayo ClinicBrian J Smith - Holden Comprehensive Cancer CenterZuhair K Ballas - Iowa City VA Medical CenterJames E Wooldridge - Department of Internal Medicine, University of IowaBrian K Link - Department of Internal Medicine, University of IowaTimothy G Call - Division of Hematology, Mayo ClinicTait D Shanafelt - Division of Hematology, Mayo ClinicDeborah A Bowen - Division of Hematology, Mayo ClinicNeil E Kay - Division of Hematology, Mayo ClinicThomas E Witzig - Division of Hematology, Mayo ClinicGeorge J Weiner - Department of Internal Medicine, University of Iowa
- Resource Type
- Journal article
- Publication Details
- Leukemia & lymphoma, Vol.53(2), pp.211-217
- DOI
- 10.3109/10428194.2011.608451
- PMID
- 21812536
- PMCID
- PMC3438221
- NLM abbreviation
- Leuk Lymphoma
- ISSN
- 1042-8194
- eISSN
- 1029-2403
- Publisher
- Taylor & Francis
- Language
- English
- Date published
- 02/01/2012
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Biostatistics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9983997325802771
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