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Open Access Research article

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

Sucheta Telang1, Mary Ann Rasku1, Amy L Clem1, Karen Carter2, Alden C Klarer1, Wesley R Badger1, Rebecca A Milam3, Shesh N Rai4, Jianmin Pan4, Hana Gragg2, Brian F Clem1, Kelly M McMasters5, Donald M Miller1 and Jason Chesney16*

Author Affiliations

1 Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA

2 Clinical Trials Office, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA

3 Department of Radiology, University of Louisville School of Medicine, Louisville, KY, USA

4 Biostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville School of Public Health, Louisville, KY, USA

5 Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA

6 James Graham Brown Cancer Center, University of Louisville, 505 South Hancock Street, #424, Louisville, KY 40202, USA

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BMC Cancer 2011, 11:515  doi:10.1186/1471-2407-11-515

Published: 13 December 2011

Abstract

Background

We 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.

Methods

In 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.

Results

After 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.

Conclusions

These 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 registration

NCT00299689