Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with everolimus (RAD001) and alemtuzumab: a Phase I/II study
Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with everolimus (RAD001) and alemtuzumab: a Phase I/II study
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使用依维莫司 (RAD001) 和阿仑单抗治疗复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤：一项 I/II 期研究
作者：
C. Zent;D. Bowen;Michael J. Conte;B. Laplant;T. Call
摘要复发/难治性慢性淋巴细胞白血病/小淋巴细胞性淋巴瘤(CLL)患者，尤其是具有嘌呤类似物难治性疾病或TP53缺失/突变的患者，在引入针对B细胞受体信号转导的治疗前预后较差。雷帕霉素(MTOR)抑制剂的哺乳动物靶点埃博利莫斯在CLL中具有生物活性，并能从淋巴组织中动员CLL细胞进入循环。在这项临床试验中，我们测定了伊维莫司的最大耐受量(MTD)和8周的皮下标准剂量阿仑珠单抗(I期)，然后评估了复发性/难治性CLL的耐受性和联合治疗的疗效(II期)。最大耐受量为2.5 mg，每周3次。依维莫司和阿伦图珠单抗的治疗可以耐受，但不够有效(33%的部分应答，没有完全应答)，建议进一步开发该方案。
Abstract Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), and especially those with purine analogue refractory disease or TP53 deletion/mutation, had a poor prognosis prior to the introduction of therapy targeting B cell receptor signaling. The mammalian target of rapamycin (mTOR) inhibitor everolimus has biological activity in CLL and can mobilize CLL cells from the lymphoid tissues into the circulation. In this clinical trial we determined the maximum tolerated dose (MTD) of everolimus together with eight weeks of standard dose subcutaneous alemtuzumab (Phase I) and then evaluated the tolerability and efficacy of therapy of relapsed/refractory CLL with the combination of everolimus and alemtuzumab (Phase II). The maximum tolerated dose of oral everolimus was 2.5 mg three times/week. Therapy with everolimus and alemtuzumab was tolerable, but not sufficiently efficacious (33% partial responses, no complete responses) to recommend further development of the regimen.
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影响因子：
20.3
作者：
Brown, Jennifer R.;Byrd, John C.;Furman, Richard R.
通讯作者：
Furman, Richard R.
DOI：
10.1056/nejmoa1315226
发表时间：
2014-03-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Furman RR;Sharman JP;Coutre SE;Cheson BD;Pagel JM;Hillmen P;Barrientos JC;Zelenetz AD;Kipps TJ;Flinn I;Ghia P;Eradat H;Ervin T;Lamanna N;Coiffier B;Pettitt AR;Ma S;Stilgenbauer S;Cramer P;Aiello M;Johnson DM;Miller LL;Li D;Jahn TM;Dansey RD;Hallek M;O'Brien SM
通讯作者：
O'Brien SM
影响因子：
15.9
作者：
Messmer, BT;Messmer, D;Chiorazzi, N
通讯作者：
Chiorazzi, N
影响因子：
20.3
作者：
Jaglowski, Samantha M.;Jones, Jeffrey A.;Byrd, John C.
通讯作者：
Byrd, John C.
影响因子：
20.3
作者：
Friedberg, Jonathan W.;Sharman, Jeff;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.