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

Abstract

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). 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 microg/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.

• Authors: 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 Stewart, K Cooper, S Stevens, F Craig, J Reuben, P Bacha, J Nichols
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 2 Pg. 376-88 (Jan 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11208829 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Diphtheria Toxin
• Interleukin-2
• Proteins
• Receptors, Interleukin-2
• Recombinant Fusion Proteins
• denileukin diftitox

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Diphtheria Toxin
• Drug Administration Schedule
• Female
• Humans
• Immunohistochemistry
• Interleukin-2
• Lymphoma, T-Cell, Cutaneous (drug therapy, metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Proteins (administration & dosage, pharmacokinetics, therapeutic use)
• Receptors, Interleukin-2 (metabolism)
• Recombinant Fusion Proteins
• Remission Induction