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

Purpose: The objective of this phase III study was to determine the efficac y, safety, and pharmacokinetics of denileukin diftitox (DAB(389)IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CAI) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other the rapeutic interventions. Patients and Methods: Patients with biopsy-proven CTCL that expressed CD25 on greater than or equal to 20% of lymphocytes were assigned to one of two dose levels (9 or 18 mug/kg/d) of denileukin diftitox administered 5 consec utive days every 3 weeks for up ta 8 cycles. Patients were monitored for to xicity and clinical efficacy, the latter assessed by changes in disease bur den and quality of life measurements. Antibody levels of antidenileukin dif titox and anti-interleukin-2 and serum concentrations of denileukin diftito x 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 resp onse). 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 ra nge of 2.7 to more than 46.1 months) were not statistically different betwe en the two doses. Adverse events consisted of flu-like symptoms (fever/chil ls, nausea/vomiting, and myalgias/arthralgias)I acute infusion-related even ts (hypotension, dyspnea, chest pain, and back pain), and a vascular leak s yndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the pati ents experienced transient elevations of hepatic transaminase levels with 1 7% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 mug/kg/d was similar, and there wa s 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 d espite other therapeutic interventions. J Clin Oncol 19:376-388. (C) 2001 b y American Society of Clinical Oncology.