Pivotal Phase III Trial of Two Dose Levels of Denileukin Diftitox for the Treatment of Cutaneous T-Cell Lymphoma

作者：Elise A. Olsen, Madeleine Duvic, Arthur E. Frankel, Youn Kim, Ann Martin, Eric C. Vonderheid, Brian V. Jegasothy, Gary S. Wood, Michael David Gordon, PETER W. HEALD, Allan Roy Oseroff, Lauren C. Pinter‐Brown, Glen M. Bowen, Timothy Michael Kuzel, David P. Fivenson, Francine M. Foss, Michael Glodé, Arturo Molina, Elizabeth H. Knobler, Stanford J. Stewart, Kevin D. Cooper, Seth R. Stevens, Fiona E. Craig, James Mwikya Reuben, Patricia Bacha, JEAN C. NICHOLS · 发表于：Journal of Clinical Oncology · 年份：2001 · DOI：10.1200/jco.2001.19.2.376 · 被引用次数：609 · 研究领域：Cutaneous lymphoproliferative disorders research、Lymphoma Diagnosis and Treatment、T-cell and Retrovirus Studies

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema)....