Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This phase II study evaluated the safety and efficacy of denileukin diftitox, an interleukin-2-diphtheria toxin fusion protein, in relapsed/refractory T-cell non-Hodgkin lymphoma (T-NHL), excluding cutaneous T-cell lymphoma. Eligible patients received denileukin diftitox 18 microg/kg/d x 5 d every 3 weeks for up to eight cycles. Tumour staging was performed every two cycles and the primary endpoint was the objective response rate [complete response (CR) + partial response (PR)]. For 27 patients enrolled, median age: 55 years (range 26-80 years), 70.4% male, and mean prior therapies: 2.5 (range 1-6). Objective responses (six CRs, seven PRs) were achieved in 13 patients (48.1%), stable disease in eight (29.6%) and six (22.2%) had progressive disease. An objective response was achieved in eight of 13 patients (61.5%) with CD25(+) tumours (four CR/four PR) and five of 11 patients (45.5%) with CD25(-) tumours (two CR/three PR). Median progression-free survival was 6 months (range, 1-38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4-5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T-NHL, with responses observed in both CD25(+) and CD25(-) tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T-NHL.
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PMID:Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. 1723 46

Denileukin diftitox plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma patients. Of the 38 evaluable patients, 30 (80%) were rituximab-refractory. The overall response rate (ORR) was 32%, with six complete responses (CR) and six partial responses (PR). The median time to progression for responders was 8 months (range: 2-36+); two patients with rituximab-refractory follicular lymphoma were in CR at 25 and 36+ months. The ORR was 55% (4 CRs, 2 PRs) in 11/14 patients with rituximab-refractory follicular lymphoma, and 100% in the three patients with rituximab-sensitive tumour. Most toxicities were low grade and transient, and myelotoxicity was uncommon.
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PMID:Phase II trial of the combination of denileukin diftitox and rituximab for relapsed/refractory B-cell non-Hodgkin lymphoma. 1760 63

Denileukin diftitox (DD) is approved for treatment of CD-25 expressing cutaneous T-cell lymphomas (CTCL). Initial studies of DD demonstrated responses in patients with B-cell non-Hodgkin lymphoma (NHL). This phase II trial evaluated response rate (RR) and tolerability of DD in this population. Patients were stratified into two arms: those with NHL expressing > or =20% IL-2R (IL-2R+) or <20% IL-2R (IL-2R-). DD was dosed at 18 microg/kg/day for 5 days every 21 days. Corticosteroid pre-medication was not allowed. Thirty-five patients of a planned 77 accrued due to closure for slow accrual. This report is on 29 patients (18 males) with indolent B-cell NHL (11 IL-2R+ and 18 IL-2R-). Histologic subtypes included small lymphocytic (SLL) (8 patients) and follicular grade I/II lymphoma (21 patients). Patients received a median of three prior regimens, including rituximab in 76%. Three partial responses were observed (RR 10%). The RR for the IL-2R- and IL-2R+ patients was 11% and 9%, respectively. Of 8 patients with SLL, 2 responded. Toxicities were generally grade I - II and transient but 1 patient experienced a fatal thrombo-embolism. Therapy with DD is tolerable and modest efficacy was observed in SLL subtype. Measured IL-2R status did not correlate with efficacy.
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PMID:Phase II study of denileukin diftitox for previously treated indolent non-Hodgkin lymphoma: final results of E1497. 1794 99

Peripheral T-cell lymphoma (PTCL) is an aggressive form of non-Hodgkin's lymphoma (NHL), associated with poor prognosis and without standard approach to treatment. Denileukin diftitox (Ontak) is a synthetic fusion protein combining the receptor-binding domain of interleukin-2 to the enzymatically active portion of diphtheria toxin. While approved for the treatment of cutaneous T-cell lymphoma, it has demonstrated activity in non-Hodgkin's lymphomas of both T-cell and B-cell origin. This report documents the first case of de novo maintenance therapy with denileukin diftitox sustaining an ongoing complete response at the molecular level for 2 years in a patient with PTCL.
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PMID:De novo maintenance therapy with denileukin diftitox (Ontak) in a patient with peripheral T-cell lymphoma is associated with prolonged remission. 1838 17

Denileukin diftitox (Ontak) is a novel recombinant fusion protein consisting of peptide sequences for the enzymatically active and membrane translocation domain of diphtheria toxin linked to human IL-2. Denileukin diftitox specifically binds to IL-2 receptors on the cell membrane, is internalized via receptor-mediated endocytosis and inhibits protein synthesis by ADP ribosylation of elongation factor 2, resulting in cell death. This article focuses on the clinical trial that led to the US FDA approval of the drug for cutaneous T-cell lymphoma in 1999, and other investigational studies for hematologic malignancies, recurrent and refractory chronic lymphocytic leukemia, non-Hodgkin B-cell lymphoma, graft-versus-host disease and autoimmune disease, demonstrating the activity and adverse effects of the drug.
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PMID:Optimizing denileukin diftitox (Ontak) therapy. 1868 57

Cutaneous T-cell lymphoma (CTCL) is a rare non-Hodgkin lymphoma with predominant skin manifestations and a relatively indolent course at early stages, but it can be fatal in advanced settings. In the absence of cure, the goal of therapy for CTCL is to induce long-term remissions without further compromising a patient's immune system or quality of life. Denileukin diftitox (DD) is a fusion protein chemotherapeutic agent used for the treatment of persistent or recurrent CTCL. It binds selectively to the high- and intermediate-affinity interleukin-2 receptor (CD25+) on lymphocytes and is internalized by these cells. Inside the cells, the diphtheria toxin portion of fusion protein is cleaved by proteolytic enzymes, causing cell death. DD produces durable responses and may forestall disease progression. This article reviews DD phase III clinical trial data and summarizes one institution's clinical experience in the management of the most frequent and clinically significant adverse effects of DD (e.g., acute infusion reactions, capillary leak syndrome, hypoalbuminemia, visual changes, constitutional symptoms, rash, hepatobiliary disorders). Many DD-associated adverse effects can be managed effectively without dose reduction or interruption of treatment with prudent use of supportive care measures.
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PMID:Adverse effects of denileukin diftitox and their management in patients with cutaneous T-cell lymphoma. 2302 42