Clinical cancer research : an official journal of the American Association for Cancer Research · 2012
A phase I dose-finding trial of recombinant interleukin-21 and rituximab in relapsed and refractory low grade B-cell lymphoproliferative disorders.
Клиническое исследование I фазыСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Timmerman John M, Byrd John C, Andorsky David J, Yamada Reiko E, Kramer Janet, Muthusamy Natarajan, Hunder Naomi, Pagel John M
Аннотация
PURPOSE: We conducted a phase I study to determine the safety, maximum-tolerated dose (MTD), and efficacy of weekly bolus recombinant human interleukin-21 (rIL-21) plus rituximab in patients with indolent B-cell malignancies.
EXPERIMENTAL DESIGN: One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy.
RESULTS: Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months).
CONCLUSIONS: Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted.
EXPERIMENTAL DESIGN: One week after a lead-in rituximab dose, cohorts of three patients were treated with 30, 100, or 150 μg/kg rIL-21 weekly for four weeks, concurrent with four weekly doses of rituximab. Patients with stable disease or better were eligible for a second course of therapy.
RESULTS: Twenty-one patients with relapsed small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL, n = 11), follicular lymphoma (n = 9), or marginal zone lymphoma (n = 1) were enrolled, with 19 completing at least one course of therapy. The MTD for rIL-21 was 100 μg/kg, based on observed toxicities including nausea, vomiting, diarrhea, hypotension, edema, and hypophosphatemia. Clinical responses were seen in 8 of 19 evaluable patients (42%; 3 CR/CRu, 5 PR), with 4 of longer duration than the patient's previous response to rituximab-based treatment (median 9 months vs. 3 months).
CONCLUSIONS: Outpatient therapy of indolent B-cell malignancies with rituximab and weekly rIL-21 was well tolerated and clinically active, with durable complete remissions in a small subset of patients. Additional studies of rIL-21 and anti-CD20 antibodies in lymphoma and SLL/CLL are warranted.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAntibodies, Monoclonal, Murine-DerivedAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFemaleHumansInterleukinsLymphoma, B-CellMaleMaximum Tolerated DoseMiddle AgedNeoplasm GradingRecombinant ProteinsRituximabInterleukin-21