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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1200/JCO.2001.19.2.376 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy and Safety of Denileukin Diftitox-Cxdl, an Improved Purity Formulation of Denileukin Diftitox, in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma.
J Clin Oncol
December 2024
Department of Dermatology, The University of Texas-MD Anderson Cancer Center, Houston, TX.
Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).
Patients And Methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles.
Compromising the immunogenicity of diphtheria toxin-based immunotoxins through epitope engineering: An in silico approach.
J Pharmacol Toxicol Methods
December 2024
Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:
Immunotoxins are genetically engineered recombinant proteins consisting of a targeting moiety, such as an antibody, and a cytotoxic toxin moiety of microbial origin. Pseudomonas exotoxin A and diphtheria toxin (DT) have been abundantly used in immunotoxins, with the latter applied as the toxin moiety of the FDA-approved drug Denileukin diftitox (ONTAK®). However, the use of immunotoxins provokes an adverse immune response in the host body against the toxin moiety, limiting their efficacy.
View Article and Find Full Text PDFIntraperitoneal immunotherapy with denileukin diftitox (ONTAK) in recurrent refractory ovarian cancer.
Gynecol Oncol
December 2024
UW Medicine Cancer Vaccine Institute, University of Washington, 850 Republican St, Seattle, WA 98195, United States of America.
Article Synopsis
- Denileukin diftitox (ONTAK) is a fusion protein that can deplete regulatory T cells, which are linked to poor outcomes in ovarian cancer, and this study aimed to assess its safety and effects when given directly into the abdomen of patients with advanced ovarian cancer.
- A phase I trial included 10 patients who received ONTAK at escalating doses, revealing a maximum tolerated dose of 15 μg/kg with mostly mild side effects, though one patient experienced a severe reaction at the highest dose.
- While some patients showed a decrease in CA-125 levels (a marker for ovarian cancer), there were no significant changes in the overall cancer response, although ONTAK successfully reduced regulatory T cells in both blood and
Novel Pharmacological Treatment Options of Steroid-Refractory Graft-versus-Host Disease.
Adv Hematol
December 2023
The Christ Hospital Network, Cincinnati, Ohio, USA.
Article Synopsis
- Graft-versus-host disease (GVHD) is a serious complication of hematopoietic stem cell transplants, with current steroid treatments being ineffective in 30-50% of cases, leading to high mortality rates in steroid-refractory GVHD (SR-GVHD).
- This review analyzes new therapeutic options for SR-GVHD, emphasizing experimental drugs like ruxolitinib, monoclonal antibodies, and other agents that show promise but require more research on their safety and effectiveness.
- While some agents demonstrate potential for improving treatment outcomes in chronic GVHD, further rigorous trials are needed to confirm their efficacy on a larger scale.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!