Clinical cancer research : an official journal of the American Association for Cancer Research · 2007
Phase 1 study of lumiliximab with detailed pharmacokinetic and pharmacodynamic measurements in patients with relapsed or refractory chronic lymphocytic leukemia.
Клиническое исследование I фазыСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Byrd John C, O'Brien Susan, Flinn Ian W, Kipps Thomas J, Weiss Mark, Rai Kanti, Lin Thomas S, Woodworth James, Wynne Dee, Reid Jennifer, Molina Arturo, Leigh Bryan, Harris Sarah
Аннотация
PURPOSE: Therapeutic antibodies have improved the outcome for patients with chronic lymphocytic leukemia (CLL). We conducted a phase 1, dose escalation and schedule optimization study of the primatized anti-CD23 antibody, lumiliximab, in patients with previously treated and refractory CLL.
EXPERIMENTAL DESIGN: Forty-six patients were assigned sequentially to cohorts 1 through 6 and received lumiliximab at 125, 250, or 375 mg/m(2) weekly for 4 weeks; 500 mg/m(2) weekly for 4 weeks [500(A)]; 500 mg/m(2) thrice during week 1 then 500 mg/m(2) weekly for the next 3 weeks [500(B)]; or 500 mg/m(2) thrice a week for 4 weeks [500(C)], respectively.
RESULTS: The median age was 62 years (range, 47-80), and the median number of prior regimens was four (range, 1-13). No partial or complete responses were observed. Toxicity was limited and unrelated to dose. The pharmacokinetics of lumiliximab was similar to other IgG(1) monoclonal antibodies with accumulation at doses > or =250 mg/m(2) and a median terminal half-life of 7 days. Pharmacodynamic studies showed dose-dependent increases in soluble CD23, but no down-regulation of CD23 antigen. Saturation of CD23 receptors occurred at 250 mg/m(2) and was maintained for > or =1 week following completion of therapy at > or =375 mg/m(2).
CONCLUSIONS: Treatment with lumiliximab seemed to be well tolerated and to have clinical activity in patients with relapsed or refractory CLL.
EXPERIMENTAL DESIGN: Forty-six patients were assigned sequentially to cohorts 1 through 6 and received lumiliximab at 125, 250, or 375 mg/m(2) weekly for 4 weeks; 500 mg/m(2) weekly for 4 weeks [500(A)]; 500 mg/m(2) thrice during week 1 then 500 mg/m(2) weekly for the next 3 weeks [500(B)]; or 500 mg/m(2) thrice a week for 4 weeks [500(C)], respectively.
RESULTS: The median age was 62 years (range, 47-80), and the median number of prior regimens was four (range, 1-13). No partial or complete responses were observed. Toxicity was limited and unrelated to dose. The pharmacokinetics of lumiliximab was similar to other IgG(1) monoclonal antibodies with accumulation at doses > or =250 mg/m(2) and a median terminal half-life of 7 days. Pharmacodynamic studies showed dose-dependent increases in soluble CD23, but no down-regulation of CD23 antigen. Saturation of CD23 receptors occurred at 250 mg/m(2) and was maintained for > or =1 week following completion of therapy at > or =375 mg/m(2).
CONCLUSIONS: Treatment with lumiliximab seemed to be well tolerated and to have clinical activity in patients with relapsed or refractory CLL.