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Melanoma: HELP
Articles by Donald M. Miller
Based on 5 articles published since 2008

Between 2008 and 2019, Donald M. Miller wrote the following 5 articles about Melanoma.
+ Citations + Abstracts
1 Clinical Trial Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma. 2011

Telang, Sucheta / Rasku, Mary Ann / Clem, Amy L / Carter, Karen / Klarer, Alden C / Badger, Wesley R / Milam, Rebecca A / Rai, Shesh N / Pan, Jianmin / Gragg, Hana / Clem, Brian F / McMasters, Kelly M / Miller, Donald M / Chesney, Jason. ·Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. ·BMC Cancer · Pubmed #22165955.

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(+)CD25(HI)Foxp3(+) 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.

2 Clinical Trial gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. 2011

Schwartzentruber, Douglas J / Lawson, David H / Richards, Jon M / Conry, Robert M / Miller, Donald M / Treisman, Jonathan / Gailani, Fawaz / Riley, Lee / Conlon, Kevin / Pockaj, Barbara / Kendra, Kari L / White, Richard L / Gonzalez, Rene / Kuzel, Timothy M / Curti, Brendan / Leming, Phillip D / Whitman, Eric D / Balkissoon, Jai / Reintgen, Douglas S / Kaufman, Howard / Marincola, Francesco M / Merino, Maria J / Rosenberg, Steven A / Choyke, Peter / Vena, Don / Hwu, Patrick. ·Indiana University Health Goshen Center for Cancer Care, Goshen, IN 46526, USA. dschwart@iuhealth.org ·N Engl J Med · Pubmed #21631324.

ABSTRACT: BACKGROUND: Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. METHODS: We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival. RESULTS: The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06). CONCLUSIONS: In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.).

3 Clinical Trial Transient T cell depletion causes regression of melanoma metastases. 2008

Rasku, Mary Ann / Clem, Amy L / Telang, Sucheta / Taft, Beverly / Gettings, Kelly / Gragg, Hana / Cramer, Daniel / Lear, Sheron C / McMasters, Kelly M / Miller, Donald M / Chesney, Jason. ·Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA. m0rask01@gwise.louisville.edu ·J Transl Med · Pubmed #18334033.

ABSTRACT: BACKGROUND: Cognate immunity against neoplastic cells depends on a balance between effector T cells and regulatory T (Treg) cells. Treg cells prevent immune attack against normal and neoplastic cells by directly suppressing the activation of effector CD4+ and CD8+ T cells. We postulated that a recombinant interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; Ontak) may serve as a useful strategy to deplete Treg cells and break tolerance against neoplastic tumors in humans. METHODS: We administered DAB/IL2 (12 microg/kg; four daily doses; 21 day cycles) to 16 patients with metastatic melanoma and measured the effects on the peripheral blood concentration of several T cell subsets and on tumor burden. RESULTS: We found that DAB/IL2 caused a transient depletion of Treg cells as well as total CD4+ and CD8+ T cells (< 21 days). T cell repopulation coincided with the de novo appearance of melanoma antigen-specific CD8+ T cells in several patients as determined by flow cytometry using tetrameric MART-1, tyrosinase and gp100 peptide/MHC conjugates. Sixteen patients received at least one cycle of DAB/IL2 and five of these patients experienced regressions of melanoma metastases as measured by CT and/or PET imaging. One patient experienced a near complete response with the regression of several hepatic and pulmonary metastases coupled to the de novo appearance of MART-1-specific CD8+ T cells. A single metastatic tumor remained in this patient and, after surgical resection, immunohistochemical analysis revealed MART1+ melanoma cells surrounded by CD8+ T cells. CONCLUSION: Taken together, these data indicate that transient depletion of T cells in cancer patients may disrupt the homeostatic control of cognate immunity and allow for the expansion of effector T cells with specificity against neoplastic cells. Several T cell depleting agents are clinically available and this study provides strong rationale for an examination of their efficacy in cancer patients. TRIAL REGISTRATION: NCT00299689 (ClinicalTrials.gov Identifier).

4 Article Pembrolizumab for Recurrent Conjunctival Melanoma. 2017

Kini, Ashwini / Fu, Roxana / Compton, Christopher / Miller, Donald M / Ramasubramanian, Aparna. ·University of Louisville, Louisville, Kentucky. ·JAMA Ophthalmol · Pubmed #28715523.

ABSTRACT: -- No abstract --

5 Article Obtaining routine blood cultures during interleukin-2-containing therapy is unnecessary. 2009

Jaglal, Michael V / Laber, Damian A / Arnold, Forest W / Miller, Donald M / Chesney, Jason A / Kloecker, Goetz H. ·Department of Medicine, University of Louisville, Louisville, KY 40202, USA. ·Am J Clin Oncol · Pubmed #19451801.

ABSTRACT: PURPOSE: To evaluate the usefulness of routine blood cultures in patients who develop temperatures of 38.5 degrees C or higher while treated with interleukin-2 (IL-2). METHODS: Retrospective chart review study. Charts of patients treated with high-dose IL-2 or biochemotherapy for metastatic melanoma were reviewed at the University of Louisville from 2005 to 2007. The study objective was to estimate the frequency of true and false positive blood cultures. RESULTS: A total of 205 blood cultures in 46 patients (27 male, 19 female) were reviewed. The average age was 53 years (25-71 years). The patients had an average of 3 cycles of therapy. The mean temperature of the febrile episodes was 38.7 degrees C. The mean absolute neutrophil count was 5.1 K/microL. Of these 205 febrile episodes, only 1 blood culture was true positive. The patient had methicillin sensitive staphylococcus aureus bacteremia. There were 5 false positive blood cultures. Four hundred thirty-four further febrile episodes were documented without blood cultures drawn. None of these patients were found to be infected. The yield of true positive blood cultures in this setting was 0.5% (0%-3%, CI). There was, however, a higher number of false positive blood cultures, 2.4% (0.5%-4.5%, CI). CONCLUSIONS: Blood cultures during IL-2 containing therapy are very inefficient to differentiate between infections versus IL-2-related fever.