TY - JOUR
T1 - Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma
AU - Olsen, E.
AU - Duvic, M.
AU - Frankel, A.
AU - Kim, Y.
AU - Martin, A.
AU - Vonderheid, E.
AU - Jegasothy, B.
AU - Wood, G.
AU - Gordon, M.
AU - Heald, P.
AU - Oseroff, A.
AU - Pinter-Brown, L.
AU - Bowen, G.
AU - Kuzel, T.
AU - Fivenson, D.
AU - Foss, F.
AU - Glode, M.
AU - Molina, A.
AU - Knobler, E.
AU - Stewart, S.
AU - Cooper, K.
AU - Stevens, S.
AU - Craig, F.
AU - Reuben, J.
AU - Bacha, P.
AU - Nichols, J.
PY - 2001/1/15
Y1 - 2001/1/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0035863468
U2 - 10.1200/JCO.2001.19.2.376
DO - 10.1200/JCO.2001.19.2.376
M3 - Article
C2 - 11208829
AN - SCOPUS:0035863468
SN - 0732-183X
VL - 19
SP - 376
EP - 388
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -