WARNING: SERIOUS INFUSION REACTIONS, CAPILLARY LEAK SYNDROME AND LOSS OF VISUAL ACUITY.
The following adverse reactions have been reported:
Serious and fatal infusion reactions. Administer Ontak in a facility equipped and staffed for cardiopulmonary resuscitation. Immediately stop and permanently discontinue Ontak for serious infusion reactions [see Warnings and Precautions (5.1)].
Capillary leak syndrome resulting in death. Monitor weight, edema, blood pressure and serum albumin levels prior to and during Ontak treatment [see Warnings and Precautions (5.2)].
Loss of visual acuity and color vision [see Warnings and Precautions (5.3)].
Ontak (denileukin diftitox), is a recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met1-Thr387)-His and the sequences for human interleukin-2 (IL-2; Ala1-Thr133). It is produced in an E. coli expression system and has a molecular weight of 58 kD. Neomycin is used in the fermentation process but is undetectable in the final product. Ontak is supplied in single use vials as a sterile, frozen solution intended for intravenous (IV) administration. Each 2 mL vial of Ontak contains 300 mcg of recombinant denileukin diftitox in a sterile solution of citric acid (20 mM), EDTA (0.05 mM) and polysorbate 20 (<1%) in Water for Injection, USP. The solution has a pH range of 6.9 to 7.2.
Ontak® is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor [see Warnings and Precautions (5.4) ].
Published Studies Related to Ontak (Denileukin Diftitox)
Phase III placebo-controlled trial of denileukin diftitox for patients with cutaneous T-cell lymphoma. [2010.04.10]
PURPOSE This phase III, placebo-controlled, randomized trial was designed to investigate efficacy and safety of two doses of denileukin diftitox (DD; DAB(389)-interleukin-2 [IL-2]), a recombinant fusion protein targeting IL-2 receptor-expressing malignant T lymphocytes, in patients with stage IA to III, CD25 assay-positive cutaneous T-cell lymphoma (CTCL), including the mycosis fungoides and Sezary syndrome forms of the disease, who had received up to three prior therapies...
Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. [2009.07.16]
Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation...
Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with denileukin diftitox (ONTAK). [2002.03]
Cutaneous T-cell lymphoma (CTCL) can be associated with painful, pruritic, disfiguring lesions. As part of a multicenter, randomized phase III trial in patients with heavily pretreated advanced and/or recurrent CTCL, the effects of an interleukin-2 receptor-targeted fusion protein, denileukin diftitox (DAB389IL-2, ONTAK), on patient-rated overall quality of life (QOL), skin appearance, and pruritus severity were evaluated...
Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. [2001.01.15]
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... 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.
NK cell adoptive transfer combined with Ontak-mediated regulatory T cell elimination induces effective adaptive antitumor immune responses. [2011.03.15]
Previous work from our laboratory showed that hydrocortisone (HC) combined with IL-15 induces expansion of activated human NK cells...
Clinical Trials Related to Ontak (Denileukin Diftitox)
ONTAK� in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment [Active, not recruiting]
RATIONALE: ONTAK may be able to help reduce the type of cells that prevent other types of
immune cells from attacking the breast cancer cells.
PURPOSE: This phase I/II trial is studying the safety of ONTAK and its possible side effects
to see how well it works in treating patients with advanced breast cancer that did not
respond to previous treatment.
A Pilot Study, Evaluating the Efficacy of Regulatory T-cell Suppression by Ontak in Metastatic Pancreatic Cancer [Terminated]
This study is designed to determine the following:
1. 1. The degree and duration of T reg suppression in patients with metastatic pancreatic
cancer receiving Ontak. The goal is to define the optimal time for future dendritic
cell vaccine administration
2. 2. To determine the safety of anti-CD4/CD25 monoclonal antibody (Ontak) in patients
with metastatic pancreatic cancer
3. 3. To follow patients treated with Ontak for a clinical response as determined by Ca
19-9 and CT scans
Ontak (Denileukin Diftitox) in Patients With Systemic Mastocytosis (SM) [Completed]
1. To assess the response rate of ONTAK in Systemic Mastocytosis (SM) patients.
1. To assess the safety of ONTAK in SM patients.
2. To evaluate the time to progression and duration of response following treatment with
A Trial of Intravenous Denileukin Diftitox in Stage III or IV Ovarian Cancer [Completed]
This study tests whether denileukin diftitox will deplete regulatory T cells, boost
tumor-specific immunity and treat epithelial ovarian cancer in patients who have failed, or
who are ineligible for front line therapy.
Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation [Terminated]
The primary goal of this study is to determine the feasibility and safety of giving two
doses of denileukin diftitox (DD) at days 0 and 21 post autologous stem cell transplantation
in a dose escalation fashion. Secondary goals include evaluating the the effect of DD on the
number and percentage of T-regs in the peripheral blood post transplant at each dose level,
the effect of DD on T cell (CD4/CD8) reconstitution post transplant at each dose level and
determining the time to engraftment: absolute neutrophil count (>0. 5 x 10^9/L for 3
consecutive days), and platelet (>20X 10^9/L for 3 consecutive days).
The hypothesis for the study is based on the ability of DD to deplete T-regs and
subsequently enhance the immune reconstitution and reverse post transplant lymphopenia. This
may indirectly enhance the efficacy of autologous transplantation and reduce disease
Reports of Suspected Ontak (Denileukin Diftitox) Side Effects
Mental Status Changes (2),
Generalised Oedema (2),
Deep Vein Thrombosis (2),
Interstitial Lung Disease (1),
Page last updated: 2011-12-09