First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial.

2.50
Hdl Handle:
http://hdl.handle.net/10541/59053
Title:
First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial.
Authors:
Hagenbeek, Anton; Gadeberg, Ole; Johnson, Peter W; Pedersen, Lars Møller; Walewski, Jan; Hellmann, Andrzej; Link, Brian K; Robak, Tadeusz; Wojtukiewicz, Marek; Pfreundschuh, Michael; Kneba, Michael; Engert, Andreas; Sonneveld, Pieter; Flensburg, Mimi; Petersen, Jørgen; Losic, Nedjad; Radford, John A ( 0000-0001-7898-2786 )
Abstract:
Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274.
Affiliation:
University Medical Center Utrecht, Department of Hematology, Utrecht, The Netherlands. a.hagenbeek@umcutrecht.nl
Citation:
First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. 2008, 111 (12):5486-95 Blood
Journal:
Blood
Issue Date:
15-Jun-2008
URI:
http://hdl.handle.net/10541/59053
DOI:
10.1182/blood-2007-10-117671
PubMed ID:
18390837
Type:
Article
Language:
en
ISSN:
1528-0020
Appears in Collections:
All Christie Publications ; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorHagenbeek, Anton-
dc.contributor.authorGadeberg, Ole-
dc.contributor.authorJohnson, Peter W-
dc.contributor.authorPedersen, Lars Møller-
dc.contributor.authorWalewski, Jan-
dc.contributor.authorHellmann, Andrzej-
dc.contributor.authorLink, Brian K-
dc.contributor.authorRobak, Tadeusz-
dc.contributor.authorWojtukiewicz, Marek-
dc.contributor.authorPfreundschuh, Michael-
dc.contributor.authorKneba, Michael-
dc.contributor.authorEngert, Andreas-
dc.contributor.authorSonneveld, Pieter-
dc.contributor.authorFlensburg, Mimi-
dc.contributor.authorPetersen, Jørgen-
dc.contributor.authorLosic, Nedjad-
dc.contributor.authorRadford, John A-
dc.date.accessioned2009-04-02T15:52:22Z-
dc.date.available2009-04-02T15:52:22Z-
dc.date.issued2008-06-15-
dc.identifier.citationFirst clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. 2008, 111 (12):5486-95 Blooden
dc.identifier.issn1528-0020-
dc.identifier.pmid18390837-
dc.identifier.doi10.1182/blood-2007-10-117671-
dc.identifier.urihttp://hdl.handle.net/10541/59053-
dc.description.abstractOfatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274.en
dc.language.isoenen
dc.subjectOfatumumaben
dc.subjectClinical Trialen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntigens, CD20-
dc.subject.meshB-Lymphocytes-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshFemale-
dc.subject.meshFollow-Up Studies-
dc.subject.meshHumans-
dc.subject.meshInfection-
dc.subject.meshKaplan-Meiers Estimate-
dc.subject.meshLymphoma, Follicular-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshRecurrence-
dc.subject.meshTreatment Outcome-
dc.titleFirst clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial.en
dc.typeArticleen
dc.contributor.departmentUniversity Medical Center Utrecht, Department of Hematology, Utrecht, The Netherlands. a.hagenbeek@umcutrecht.nlen
dc.identifier.journalBlooden

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