Journal of hematology & oncology · 2014
A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors.
Клиническое исследование II фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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de Vos Sven, Forero-Torres Andres, Ansell Stephen M, Kahl Brad, Cheson Bruce D, Bartlett Nancy L, Furman Richard R, Winter Jane N, Kaplan Henry, Timmerman John, Whiting Nancy C, Drachman Jonathan G, Advani Ranjana
Аннотация
BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study.
METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies.
RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity.
CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916.
METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies.
RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3-4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3-4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity.
CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916.
Предметные рубрики MeSH
AdolescentAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedCD40 AntigensChillsDose-Response Relationship, DrugDrug Administration ScheduleFatigueFemaleHeadacheHumansKaplan-Meier EstimateLymphoma, Large B-Cell, DiffuseLymphopeniaMaleMiddle AgedNeoplasm Recurrence, LocalPolymorphism, Single NucleotideReceptors, IgGRemission InductionTreatment OutcomeYoung Adult