title: 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 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.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. zent.clive@mayo.edu
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Zuhair K
authors.initials: ZK
authors.lastname: Ballas
authors.forename: James E
authors.initials: JE
authors.lastname: Wooldridge
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Bowen
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: George J
authors.initials: GJ
authors.lastname: Weiner
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D011379:Prognosis; D016879:Salvage Therapy
chemical_list: D009838:Oligodeoxyribonucleotides; C483020:ProMune