The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Paul A Carpenter - One of the best experts on this subject based on the ideXlab platform.
-
a phase ii multicenter study of Visilizumab humanized anti cd3 antibody to treat steroid refractory acute graft versus host disease
Biology of Blood and Marrow Transplantation, 2005Co-Authors: Paul A Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, H Khoury, Pablo Parker, Keith R Jerome, Jeannine S MccuneAbstract:Abstract Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody Visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which Visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of Visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
-
a humanized non fcr binding anti cd3 antibody Visilizumab for treatment of steroid refractory acute graft versus host disease
Blood, 2002Co-Authors: Paul A Carpenter, Frederick R Appelbaum, Lawrence Corey, Joachim H Deeg, Kris Doney, Ted Gooley, James Krueger, Paul J Martin, Sandra Pavlovic, J E SandersAbstract:Visilizumab is a humanized anti-CD3 monoclonal antibody characterized by a mutated IgG2 isotype, lack of binding to Fcγ-receptors, and ability to induce apoptosis selectively in activated T cells. To test pharmacokinetics, safety, and immunosuppressive activity of Visilizumab, 17 patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD) were enrolled in a phase 1 study. Six patients were given 7 doses of Visilizumab (0.25 or 1.0 mg/m2) on days 1, 3, 5, 7, 9, 11, and 13. Because multiple doses of 1 mg/m2 caused delayed Visilizumab accumulation and prolonged lymphopenia, the next 11 patients received a single dose of 3.0 mg/m2 on day 1. GVHD improved in all patients; 15 were evaluable through day 42. Multiple dosing resulted in 1 of 6 complete responses (CRs) and 5 partial responses (PRs), but all 6 patients died at a median of 87 days after starting Visilizumab therapy. Single dosing resulted in 6 of 9 CRs, 3 PRs, and 7 of 11 patients surviving after 260 to 490 days (median, 359 days; P = .03). There were no allergic reactions and 3 grade 1 acute infusional toxicities. Plasma Epstein-Barr virus (EBV) DNA titers more than 1000 copies/mL and posttransplant lymphoproliferative disease (PTLD) developed in 2 of the first 7 patients. Based on rising EBV DNA titers, 5 of the next 10 patients were given the B cell–specific monoclonal antibody, rituximab. EBV DNA became undetectable and no overt PTLD developed. Visilizumab is well tolerated and has activity in advanced GVHD. A phase 2 study incorporating preemptive therapy for PTLD is warranted to determine the efficacy of Visilizumab in GVHD.
Scott E Plevy - One of the best experts on this subject based on the ideXlab platform.
-
anti cd3 antibody Visilizumab is not effective in patients with intravenous corticosteroid refractory ulcerative colitis
Gut, 2010Co-Authors: William J Sandborn, Scott E Plevy, Daniel W Hommes, Lloyd Mayer, Jeanfrederic Colombel, Matthew Frankel, James N Lowder, Pieter C F Stokkers, Simon Travis, G Van AsscheAbstract:Background and aims Pilot studies with Visilizumab, a humanised monoclonal antibody to CD3, suggest efficacy for corticosteroid-refractory ulcerative colitis (UC). A placebo-controlled trial was warranted. Methods A randomised, double-blind, placebocontrolled study evaluated the efficacy of Visilizumab induction treatment in 127 patients with severely active UC despite treatment with $5 days of intravenous corticosteroids. Patients received placebo or Visilizumab 5 mg/kg intravenously on days 1 and 2. Corticosteroids were tapered according to disease activity. Patients were followed up for 90 days. The primary end point was induction of response at day 45. Secondary end points included remission and mucosal healing at day 45, symptomatic response at day 15 and colectomy. Results Response at day 45 occurred in 55% of patients receiving Visilizumab compared with 47% of those who received placebo (p¼0.475). Remission at day 45 occurred in 8% of patients receiving Visilizumab compared with 9% of those who received placebo (p¼0.704). Mucosal healing at day 45 occurred in 29% of patients receiving Visilizumab compared with 26% of those who received placebo (p¼0.799). Symptomatic response at day 15 occurred in 82% of patients receiving Visilizumab compared with 74% of those who received placebo (p¼0.244). Colectomy was performed in 18% of patients receiving Visilizumab compared with 7% of those who received placebo (p¼0.130). Cardiac disorders and vascular disorders occurred more frequently in the patients who received Visilizumab. Conclusion Visilizumab at a dose of 5 mg/kg for two consecutive days was not effective for severe, corticosteroid-refractory UC and was associated with increased cardiac and vascular adverse events. (Registered at http://www.clinicaltrials. govNCT00279422/).
-
prospective randomized open label multicenter phase i ii dose escalation trial of Visilizumab hum291 in severe steroid refractory ulcerative colitis
Inflammatory Bowel Diseases, 2010Co-Authors: Daniel C Baumgart, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma Mahadevan, Axel Dignass, Gert Van Assche, D W Hommes, Walter Reinisch, Scott E PlevyAbstract:Background: Visilizumab is a humanized IgG2 monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC). Methods: In all, 104 patients were treated. In Stage I, 73 patients were randomly assigned to receive intravenous Visilizumab 5, 7.5, 10, or 12.5 μg/kg/day for 2 consecutive days. In Stage II, 33 patients received Visilizumab at the optimal clinical dose (OCD) of 5 μg/kg/day for 2 days. Symptomatic response and remission were defined by the modified Truelove–Witts severity index. Clinical response and remission were defined by the Mayo score. Results: The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 μg/kg dose groups were 71%, 70%, 50%, and 61%, respectively, in Stage I and in 54% in Stage II. The symptomatic remission rates were 35%, 5%, 22%, and 11% in Stage I and 18% in Stage II. The rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 μg/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in Stage I and 55% in Stage II. The clinical remission rates were 6%, 5%, 0%, and 11% in Stage I and 6% in Stage II. All patients experienced adverse events. Serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis. Conclusions: Treatment with Visilizumab induced symptomatic response and clinical response. Results with 5 μg/kg/day were similar to those observed with higher doses (NCT00267306 at www.clinicaltrials.gov). (Inflamm Bowel Dis 2009;)
-
a phase i study of Visilizumab a humanized anti cd3 monoclonal antibody in severe steroid refractory ulcerative colitis
Gastroenterology, 2007Co-Authors: Scott E Plevy, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel W Hommes, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma MahadevanAbstract:Background & Aims: To evaluate the safety and biological activity of Visilizumab (a humanized anti-CD3 monoclonal antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received Visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index 30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid–refractory ulcerative colitis.
-
a humanized anti cd3 monoclonal antibody Visilizumab for treatment of severe steroid refractory ulcerative colitis preliminary results of a phase i study
Gastroenterology, 2003Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian WaltersAbstract:Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized anti-CD3 monoclonal antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of Visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of <3) and an endoscopy score of 0 or 1. Patients have continued to maintain clinical improvement for several months following treatment. The first 3 patients are now beyond 90 days and have been tapered off steroids onto 5-ASA's or are receiving no additional therapy. Transient (1-4 week) decreases in T-lymphocyte counts from peripheral blood were observed. Moderate cytokine release symptoms (nausea, vomiting, chifis, arthmlgias) were observed in four patients, and one patient had severe dehydration that required fluid support. These symptoms were transient, resolving within 1-2 hours and occurred predominantly on day 1. Two patients had transienL low-level Epstein-Barr titers (3640, 5153 copies/m1) in whole-blood detected by PCR that were not associated with clinical symptoms. There have been no documented infectious complications. Conclusions: This preliminary analysis of an open-label phase [ study of Visilizumab in patients with severe UC has demonstrated potential tolerahility and clinical activity at a very low dose. Enrollment into this study continues and the data will be updated at the meeting.
Jeannine S Mccune - One of the best experts on this subject based on the ideXlab platform.
-
a phase ii multicenter study of Visilizumab humanized anti cd3 antibody to treat steroid refractory acute graft versus host disease
Biology of Blood and Marrow Transplantation, 2005Co-Authors: Paul A Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, H Khoury, Pablo Parker, Keith R Jerome, Jeannine S MccuneAbstract:Abstract Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody Visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which Visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of Visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
Stephan R Targan - One of the best experts on this subject based on the ideXlab platform.
-
prospective randomized open label multicenter phase i ii dose escalation trial of Visilizumab hum291 in severe steroid refractory ulcerative colitis
Inflammatory Bowel Diseases, 2010Co-Authors: Daniel C Baumgart, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma Mahadevan, Axel Dignass, Gert Van Assche, D W Hommes, Walter Reinisch, Scott E PlevyAbstract:Background: Visilizumab is a humanized IgG2 monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC). Methods: In all, 104 patients were treated. In Stage I, 73 patients were randomly assigned to receive intravenous Visilizumab 5, 7.5, 10, or 12.5 μg/kg/day for 2 consecutive days. In Stage II, 33 patients received Visilizumab at the optimal clinical dose (OCD) of 5 μg/kg/day for 2 days. Symptomatic response and remission were defined by the modified Truelove–Witts severity index. Clinical response and remission were defined by the Mayo score. Results: The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 μg/kg dose groups were 71%, 70%, 50%, and 61%, respectively, in Stage I and in 54% in Stage II. The symptomatic remission rates were 35%, 5%, 22%, and 11% in Stage I and 18% in Stage II. The rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 μg/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in Stage I and 55% in Stage II. The clinical remission rates were 6%, 5%, 0%, and 11% in Stage I and 6% in Stage II. All patients experienced adverse events. Serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis. Conclusions: Treatment with Visilizumab induced symptomatic response and clinical response. Results with 5 μg/kg/day were similar to those observed with higher doses (NCT00267306 at www.clinicaltrials.gov). (Inflamm Bowel Dis 2009;)
-
transient cytokine induced liver injury following administration of the humanized anti cd3 antibody Visilizumab hum291 in crohn s disease
The American Journal of Gastroenterology, 2009Co-Authors: Daniel C Baumgart, William J Sandborn, Stephan R Targan, James N Lowder, Matthew FrankelAbstract:Transient Cytokine-Induced Liver Injury Following Administration of the Humanized Anti-CD3 Antibody Visilizumab (HuM291) in Crohn's Disease
-
a phase i study of Visilizumab a humanized anti cd3 monoclonal antibody in severe steroid refractory ulcerative colitis
Gastroenterology, 2007Co-Authors: Scott E Plevy, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel W Hommes, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Uma MahadevanAbstract:Background & Aims: To evaluate the safety and biological activity of Visilizumab (a humanized anti-CD3 monoclonal antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received Visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index 30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid–refractory ulcerative colitis.
-
a humanized anti cd3 monoclonal antibody Visilizumab for treatment of severe steroid refractory ulcerative colitis preliminary results of a phase i study
Gastroenterology, 2003Co-Authors: Scott E Plevy, Bruce Salzberg, Miguel Regueiro, William J Sandborn, Stephen B Hanauer, Stephan R Targan, Lloyd Mayer, Ian WaltersAbstract:Purpose: In severe, steroid-resistant ulcerative colitis (UC), therapeutic approaches have involved targeting T-cells to control excess inflammation. We hypothesize that the humanized anti-CD3 monoclonal antibody, visiliaumab (Protein Design Labs, Inc., Fremont, CA), may provide therapeutic benefit in UC Methods: We report preliminary results from multicenter, phase I dose-escalation study of visilianmab in patients with severe UC whose disease has not responded to a minimum of 5 days of intravenous (IV) corticosteroids. Seven patients have been enrolled to date; five patients (reported here) have passed the day 30 evaluation. All patients received an IV infusion of Visilizumab at 15 p,/kg on study days 1 and 2. Results: At enrollment, the first 5 patients had a median modified Truelove and Witts (MTWS]) score of 13 (range 11-16); all had an endoscopy score of 3 (scale 0-3, 3 = severe disease), with >60 cm of colon involvement by endoscopy. At day 30, these 5 patients all achieved clinical and endoscopic remLssion (defined as an MTWSI of <3) and an endoscopy score of 0 or 1. Patients have continued to maintain clinical improvement for several months following treatment. The first 3 patients are now beyond 90 days and have been tapered off steroids onto 5-ASA's or are receiving no additional therapy. Transient (1-4 week) decreases in T-lymphocyte counts from peripheral blood were observed. Moderate cytokine release symptoms (nausea, vomiting, chifis, arthmlgias) were observed in four patients, and one patient had severe dehydration that required fluid support. These symptoms were transient, resolving within 1-2 hours and occurred predominantly on day 1. Two patients had transienL low-level Epstein-Barr titers (3640, 5153 copies/m1) in whole-blood detected by PCR that were not associated with clinical symptoms. There have been no documented infectious complications. Conclusions: This preliminary analysis of an open-label phase [ study of Visilizumab in patients with severe UC has demonstrated potential tolerahility and clinical activity at a very low dose. Enrollment into this study continues and the data will be updated at the meeting.
Keith R Jerome - One of the best experts on this subject based on the ideXlab platform.
-
a phase ii multicenter study of Visilizumab humanized anti cd3 antibody to treat steroid refractory acute graft versus host disease
Biology of Blood and Marrow Transplantation, 2005Co-Authors: Paul A Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, H Khoury, Pablo Parker, Keith R Jerome, Jeannine S MccuneAbstract:Abstract Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody Visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which Visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of Visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.
