Journal article
Phase i trial of toll-like receptor 9 agonist PF-3512676 with and following rituximab in patients with recurrent indolent and aggressive non -Hodgkin's lymphoma
Clinical cancer research, Vol.13(20), pp.6168-6174
2007
DOI: 10.1158/1078-0432.CCR-07-0815
PMID: 17947483
Abstract
Purpose: PF-3512676 (formerly CpG 7909) is a novel Toll-like receptor 9-activating oligonucleotide with single-agent antitumor activity that augments preclinical rituximab efficacy. This Phase I trial was designed to investigate the safety, tolerability, and preliminary antitumor activity of PF-3512676 in combination with rituximab.
Experimental design: Patients with relapsed/refractory CD20+ B cell non-Hodgkin's lymphoma received i.v. rituximab (375 mg/m2/week for 4 weeks) and PF-3512676 weekly for 4 weeks either i.v. (0.04, 0.16, 0.32, or 0.48 mg/kg) or s.c. (0.01, 0.04, 0.08, or 0.16 mg/kg). An additional extended-treatment cohort received 4 weeks of 0.24 mg/kg s.c. PF-3512676 in combination with rituximab followed by s.c. PF-3512676 alone weekly for 20 weeks.
Results: Patients (N = 50) had received a median of three prior therapies (range, 1-11) including rituximab in 80% of patients. Treatment-related adverse events occurred in 11 of 19 (58%) i.v. patients, 15 of 19 (79%) s.c. patients, and all 12 patients in the extended-treatment cohort. Most common adverse events were mild to moderate systemic flu-like symptoms and injection-site reactions (s.c. cohorts only). Grade 3/4 neutropenia occurred in four patients. Objective responses occurred in 12 of 50 (24%) patients overall and in 6 of 12 (50%) patients in the extended-treatment cohort, including 2 patients with rituximab-refractory disease.
Conclusion: Brief or extended-duration PF-3512676 can be safely administered in combination with rituximab in patients with relapsed/refractory non-Hodgkin's lymphoma.
Details
- Title: Subtitle
- Phase i trial of toll-like receptor 9 agonist PF-3512676 with and following rituximab in patients with recurrent indolent and aggressive non -Hodgkin's lymphoma
- Creators
- John P LEONARD - Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York, United StatesBrian K LINK - University of Iowa, Iowa City, Iowa, United StatesArthur M KRIEG - Coley Pharmaceutical Group, Inc, Wellesley, Massachusetts, United StatesGeorge J WEINER - University of Iowa, Iowa City, Iowa, United StatesChristos EMMANOUILIDES - University of California at Los Angeles Medical Center, Los Angeles, California, United StatesStephanie A GREGORY - Rush -Presbyterian -St. Luke's Medical Center, Chicago, Illinois, United StatesDaniel WEISDORF - University of Minnesota, Minneapolis, Minnesota, United StatesJeffrey ANDREY - Scripps Clinic, La Jolla, California, United StatesJohn HAINSWORTH - Sarah Cannon Cancer Center, Nashville, Tennessee, United StatesJoseph A SPARANO - Montefiore-Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York, United StatesDonald E TSAI - University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, United StatesSandra HORNING - Stanford University Medical Center, Palo Alto, California, United States
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.13(20), pp.6168-6174
- DOI
- 10.1158/1078-0432.CCR-07-0815
- PMID
- 17947483
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- American Association for Cancer Research
- Language
- English
- Date published
- 2007
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094377702771
Metrics
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