Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma

E. Olsen, M. Duvic, A. Frankel, Y. Kim, A. Martin, E. Vonderheid, B. Jegasothy, G. Wood, M. Gordon, P. Heald, A. Oseroff, L. Pinter-Brown, G. Bowen, T. Kuzel, D. Fivenson, F. Foss, M. Glode, A. Molina, E. Knobler, S. StewartK. Cooper, S. Stevens, F. Craig, J. Reuben, P. Bacha, J. Nichols

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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 ≥ 20% of lymphocytes were assigned to one or two dose levels (9 or 18 μg/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). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 μg/kg/d was similar, and there was no evidence of cumulative toxicity. Conclusion: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)376-388
Number of pages13
JournalJournal of Clinical Oncology
Issue number2
StatePublished - Jan 15 2001


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Olsen, E., Duvic, M., Frankel, A., Kim, Y., Martin, A., Vonderheid, E., Jegasothy, B., Wood, G., Gordon, M., Heald, P., Oseroff, A., Pinter-Brown, L., Bowen, G., Kuzel, T., Fivenson, D., Foss, F., Glode, M., Molina, A., Knobler, E., ... Nichols, J. (2001). Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. Journal of Clinical Oncology, 19(2), 376-388. https://doi.org/10.1200/JCO.2001.19.2.376