Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

BMC Cancer

Research Article

Jianmin Pan¹  Shesh N Rai¹  Karen Carter²  Hana Gragg²  Rebecca A Milam³  Kelly M McMasters⁴  Alden C Klarer⁵  Mary Ann Rasku⁵  Donald M Miller⁵  Wesley R Badger⁵  Brian F Clem⁵  Sucheta Telang⁵  Amy L Clem⁵  Jason Chesney⁶ 

[1] Biostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville School of Public Health, Louisville, KY, USA;Clinical Trials Office, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA;Department of Radiology, University of Louisville School of Medicine, Louisville, KY, USA;Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA;Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA;Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA;James Graham Brown Cancer Center, University of Louisville, 505 South Hancock Street, #424, 40202, Louisville, KY, USA;

关键词: Melanoma;    Treg Cell;    Melanoma Patient;    Ipilimumab;    Vitiligo;   

DOI  :  10.1186/1471-2407-11-515

 received in 2011-06-21, accepted in 2011-12-13,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundWe previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4+CD25HIFoxp3+ regulatory T cells and expanded melanoma-specific CD8+ T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.MethodsIn a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[18 F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.ResultsAfter DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.ConclusionsThese data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.Trial registrationNCT00299689

【 授权许可】

Unknown   
© Telang et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.