Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Heather Horne is active.

Publication


Featured researches published by Heather Horne.


Journal of Clinical Oncology | 2005

Combination antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma

John P. Leonard; Morton Coleman; Jamie Ketas; Michelle Ashe; J. M. Fiore; Richard R. Furman; Ruben Niesvizky; Tsiporah Shore; Amy Chadburn; Heather Horne; Jacqueline Kovacs; Cliff Ding; William A. Wegener; Ivan Horak; David M. Goldenberg

PURPOSE To explore the safety and therapeutic activity of combination anti-B-cell monoclonal antibody therapy in non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate-risk or high-risk International Prognostic Index scores. All patients were rituximab naïve. RESULTS Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months. CONCLUSION The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.


Clinical Cancer Research | 2005

Dose-Fractionated Radioimmunotherapy in Non-Hodgkin's Lymphoma Using DOTA-Conjugated, 90Y-Radiolabeled, Humanized Anti-CD22 Monoclonal Antibody, Epratuzumab.

Ola Lindén; Cecilia Hindorf; Eva Cavallin-Ståhl; William A. Wegener; David M. Goldenberg; Heather Horne; Tomas G Ohlsson; Lars Stenberg; Sven-Erik Strand; Jan Tennvall

Purpose: Fractionated radioimmunotherapy may improve therapeutic outcome by decreasing heterogeneity of the dose delivered to the tumor and by decreasing hematologic toxicity, thereby allowing an increased amount of radionuclide to be administered. Because humanized anti-CD22 epratuzumab can be given repeatedly, a single-center study was conducted to establish the feasibility, safety, optimal dosing, and preliminary efficacy of weekly administrations of 90Y-labeled 1,4,7,10-tetra-azacyclodecane-N,N′,N″,N‴-tetraacetic acid–conjugated epratuzumab. Experimental Design: Cohorts of three to six patients with B-cell lymphoma received 185 MBq/m2 [90Y]epratuzumab with unconjugated epratuzumab (total protein dose 1.5 mg/kg) once weekly for two to four infusions, with [111In]epratuzumab coadministered at first infusion for scintigraphic imaging and dosimetry. Results: Sixteen patients received treatment without significant infusional reactions. The overall objective response rate was 62% (95% confidence interval, 39-86%) in both indolent (75%) and aggressive disease (50%). Complete responses (CR/CRu) occurred in 25% of patients and were durable (event-free survival, 14-41 months). Two patients receiving four infusions had hematologic dose-limiting toxicity. Serum epratuzumab levels increased with each weekly dose. Of 13 patients with tumor cell CD22 expression determined by flow cytometry, seven of eight with strongly positive results had objective responses, versus one of five with negative or weakly positive results (P = 0.032). Conclusions: Radioimmunotherapy with weekly 185 MBq/m2 [90Y]epratuzumab achieved a high objective response rate (62%) across lymphoma subtypes, including durable CRs. The findings that three weekly infusions (555 MBq/m2, total dose) can be administered safely with only minor toxicity, that antibody levels increased during treatment weeks, and that therapeutic response predominantly occurs in patients with unequivocal CD22 tumor expression provide guidance for future studies.


Journal of Clinical Oncology | 2010

High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

Franck Morschhauser; Françoise Kraeber-Bodéré; William A. Wegener; Jean-Luc Harousseau; Marie-Odile Petillon; Damien Huglo; Lorenz Trümper; Johannes Meller; Michael Pfreundschuh; Carl-Martin Kirsch; Ralph Naumann; Joachim Kropp; Heather Horne; Nick Teoh; Steven Le Gouill; Caroline Bodet-Milin; Jean-François Chatal; David M. Goldenberg

PURPOSE Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. CONCLUSION Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.


Cancer | 2012

Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial

Allyson J. Ocean; Kenneth Pennington; Michael J. Guarino; Arif Sheikh; Tanios Bekaii-Saab; Aldo N. Serafini; Daniel Lee; Max W. Sung; Seza Gulec; Stanley J. Goldsmith; Timothy Manzone; Michael Holt; Bert H. O'Neil; Nathan Hall; Alberto J. Montero; John Kauh; David V. Gold; Heather Horne; William A. Wegener; David M. Goldenberg

It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single‐dose yttrium‐90‐labeled hPAM4 (90Y‐hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low‐dose gemcitabine in this disease.


Haematologica | 2011

Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma

George O. Negrea; Rebecca Elstrom; Steven L. Allen; Kanti R. Rai; Rashid M. Abbasi; Charles M. Farber; Nick Teoh; Heather Horne; William A. Wegener; David M. Goldenberg

Background Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. Design and Methods A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2nd generation anti-CD20 antibody veltuzumab in patients with CD20+ indolent non-Hodgkin’s lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Conclusions Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin’s lymphoma. (Clinicaltrials.gov identifier: NCT00546793)


Clinical Cancer Research | 2011

Treatment of Advanced Pancreatic Carcinoma with 90Y-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial

Seza A. Gulec; Steven J. Cohen; Kenneth L. Pennington; Lionel S. Zuckier; Ralph J. Hauke; Heather Horne; William A. Wegener; Nick Teoh; David V. Gold; Robert M. Sharkey; David M. Goldenberg

Purpose: Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of 90Y-clivatuzumab tetraxetan (90Y-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design: Twenty-one patients (4 stage III; 17 stage IV) received 111In-hPAM4 for imaging and serum sampling before 90Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results:111In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before 90Y-hPAM4; otherwise, 20 patients received 90Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m2 (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with 90Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m2 encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m2 as the maximal tolerated 90Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%–52% tumor diameter shrinkage). Conclusion:90Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated 90Y dose, and is a potential new therapeutic for advanced pancreatic cancer. Clin Cancer Res; 17(12); 4091–100. ©2011 AACR.


British Journal of Haematology | 2013

Phase I, multicentre, dose-escalation trial of monotherapy with milatuzumab (humanized anti-CD74 monoclonal antibody) in relapsed or refractory multiple myeloma.

Jonathan L. Kaufman; Ruben Niesvizky; Edward A. Stadtmauer; Asher Chanan-Khan; David Siegel; Heather Horne; William A. Wegener; David M. Goldenberg

CD74, expressed in multiple myeloma (MM), was evaluated as a target for immunotherapy with milatuzumab (a humanized anti‐CD74 antibody). In a multicentre dose escalation study, 25 patients with advanced MM received milatuzumab doses of 1·5 (N = 8), 4·0 (N = 9), 8·0 (N = 4) or 16·0 mg/kg (N = 4) administered twice weekly x 4. They had a median of 5 prior treatments (17 post ≥1 stem cell transplantation) and were refractory (N = 7) or relapsed (N = 18) with generally short‐lived responses to last treatment (median 4·0 months). After increasing prophylactic medications and slowing administration, infusions were well tolerated (National Cancer Institute‐Common Terminology Criteria v3 toxicity Grades 1–2) with no dose‐limiting toxicity at higher doses. Only one patient developed borderline positive human anti‐milatuzumab antibody titres of uncertain clinical significance. Although milatuzumab was rapidly cleared from circulation with little serum accumulation and low trough levels, B‐cell levels were moderately decreased with treatment (median decrease, 34%). There were no objective responses by European Group for Blood and Marrow Transplantation criteria, but 5 of 19 patients (26%) who completed treatment in this heavily pretreated and generally refractory group had stable disease for ≥3 months post‐treatment (one continuing for 17 months). Disease stabilization and evidence of pharmacodynamic activity support further development for use in combination with other agents or as a drug conjugate. (Clinicaltrials.gov identifier: NCT00421525)


British Journal of Haematology | 2013

Low-dose anti-CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study

Howard A. Liebman; Mansoor N. Saleh; James B. Bussel; Ovidiu George Negrea; Heather Horne; William A. Wegener; David M. Goldenberg

Low doses of the humanized anti‐CD20 monoclonal antibody, veltuzumab, were evaluated in 41 patients with immune thrombocytopenia (ITP), including 9 with ITP ≤1 year duration previously treated with steroids and/or immunoglobulins, and 32 with ITP >1 year and additional prior therapies. They received two doses of 80–320 mg veltuzumab 2 weeks apart, initially by intravenous (IV) infusion (N = 7), or later by subcutaneous (SC) injections (N = 34), with only one Grade 3 infusion reaction and no other safety issues. Thirty‐eight response‐assessable patients had 21 (55%) objective responses (platelet count ≥30 × 109/l and ≥2 × baseline), including 11 (29%) complete responses (CRs) (platelet count ≥100 × 109/l). Responses (including CRs) occurred with both IV and SC administration, at all veltuzumab dose levels, and regardless of ITP duration. Responders with ITP ≤1 year had a longer median time to relapse (14·4 months) than those with ITP >1 year (5·8 months). Three patients have maintained a response for up to 4·3 years. SC injections resulted in delayed and lower peak serum levels of veltuzumab, but B‐cell depletion occurred after first administration even at the lowest doses. Eight patients, including 6 responders, developed anti‐veltuzumab antibodies following treatment (human anti‐veltuzumab antibody, 19·5%). Low‐dose SC veltuzumab appears convenient, well‐tolerated, and with promising clinical activity in relapsed ITP.(Clinicaltrials.gov identifier: NCT00547066.)


Leukemia & Lymphoma | 2016

Subcutaneous injections of low doses of humanized anti-CD20 veltuzumab: a phase I study in chronic lymphocytic leukemia*

Matt Kalaycio; O George Negrea; Steven L. Allen; Kanti R. Rai; Rashid M. Abbasi; Heather Horne; William A. Wegener; David M. Goldenberg

Abstract To evaluate the potential of subcutaneous (SC) injections with anti-CD20 antibody veltuzumab in chronic lymphocytic leukemia (CLL), 21 patients received 80, 160, or 320 mg injections every 2 weeks × 4 doses (n = 11) or 160 or 320 mg twice-weekly × 16 doses (n = 10). Treatment was well tolerated with only occasional, mild-moderate, transient injection reactions. Lymphocytosis decreased in all patients (maximum decrease, 5–91%), with 12 patients obtaining >50% decreases. Of 14 patients with lymphadenopathy on CT imaging, 5 (36%) achieved 14–61% reductions (sum of perpendicular diameters). By NCI-WG criteria, two patients achieved partial responses (10%). SC veltuzumab appeared active in all dose groups, with no obvious exposure-response relationship, despite cumulative doses ranging from 320–5120 mg. Overall median progression-free survival was 7.7 months; three patients remained progression-free >1 year (2 ongoing at 2-year study completion). These data suggest further studies of SC veltuzumab in CLL are warranted.


European Journal of Cancer | 2015

90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

Vincent J. Picozzi; Ramesh K. Ramanathan; Maeve Aine Lowery; Allyson J. Ocean; Edith P. Mitchel; Bert H. O’Neil; Michael J. Guarino; Paul Conkling; Steven J. Cohen; Nathan Bahary; Richard C. Frank; Tomislav Dragovich; Benjamin B. Bridges; Fadi S. Braiteh; Alexander Starodub; Fa-Chyi Lee; Thomas E. Gribbin; Donald A. Richards; Marie Lee; Ronald L. Korn; Neeta Pandit-Taskar; Stanley J. Goldsmith; Charles M. Intenzo; Arif Sheikh; Timothy C. Manzone; Heather Horne; Robert M. Sharkey; William A. Wegener; Eileen M. O’Reilly; David M. Goldenberg

BACKGROUND For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year. CONCLUSIONS Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.

Collaboration


Dive into the Heather Horne's collaboration.

Top Co-Authors

Avatar

David M. Goldenberg

Pennsylvania State University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Nick Teoh

Roswell Park Cancer Institute

View shared research outputs
Top Co-Authors

Avatar

David V. Gold

University of Rochester Medical Center

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Mansoor N. Saleh

University of Alabama at Birmingham

View shared research outputs
Top Co-Authors

Avatar

Charles M. Farber

Memorial Hospital of South Bend

View shared research outputs
Top Co-Authors

Avatar

Howard A. Liebman

University of Southern California

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge