title: Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Duke University Medical Center, Durham, NC 27710, USA. olsen001@mc.duke.edu
authors.forename: E
authors.initials: E
authors.lastname: Olsen
authors.forename: M
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authors.lastname: Duvic
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authors.initials: A
authors.lastname: Frankel
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authors.initials: Y
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: E
authors.initials: E
authors.lastname: Vonderheid
authors.forename: B
authors.initials: B
authors.lastname: Jegasothy
authors.forename: G
authors.initials: G
authors.lastname: Wood
authors.forename: M
authors.initials: M
authors.lastname: Gordon
authors.forename: P
authors.initials: P
authors.lastname: Heald
authors.forename: A
authors.initials: A
authors.lastname: Oseroff
authors.forename: L
authors.initials: L
authors.lastname: Pinter-Brown
authors.forename: G
authors.initials: G
authors.lastname: Bowen
authors.forename: T
authors.initials: T
authors.lastname: Kuzel
authors.forename: D
authors.initials: D
authors.lastname: Fivenson
authors.forename: F
authors.initials: F
authors.lastname: Foss
authors.forename: M
authors.initials: M
authors.lastname: Glode
authors.forename: A
authors.initials: A
authors.lastname: Molina
authors.forename: E
authors.initials: E
authors.lastname: Knobler
authors.forename: S
authors.initials: S
authors.lastname: Stewart
authors.forename: K
authors.initials: K
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Stevens
authors.forename: F
authors.initials: F
authors.lastname: Craig
authors.forename: J
authors.initials: J
authors.lastname: Reuben
authors.forename: P
authors.initials: P
authors.lastname: Bacha
authors.forename: J
authors.initials: J
authors.lastname: Nichols
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004167:Diphtheria Toxin; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011506:Proteins; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox