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

• DOI: 10.1200/jco.2001.19.2.376
• Publication Date: 2017-02-24T07:36:55Z
• Authors: Elise Olsen; Madeleine Duvic; Arthur Frankel; Youn Kim; Ann Martin; Eric Vonderheid; Brian Jegasothy; Gary Wood; Michael Gordon; Peter Heald; Allan Oseroff; Lauren Pinter-Brown; Glen Bowen; Timothy Kuzel; David Fivenson; Francine Foss; Michael Glode; Arturo Molina; Elizabeth Knobler; Stanford Stewart; Kevin Cooper; Seth Stevens; Fiona Craig; James Reuben; Patricia Bacha; Jean Nichols
• Keywords: Adult; Aged, 80 and over; Male; Recombinant Fusion Proteins; Remission Induction; Proteins; Antineoplastic Agents; Receptors, Interleukin-2; Middle Aged; Immunohistochemistry; Drug Administration Schedule; Lymphoma, T-Cell, Cutaneous; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Humans; Interleukin-2; Diphtheria Toxin; Female; Aged; Neoplasm Staging

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Phar-maceuticals 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 of 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.