Phase I Trial of Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox (CAT-8015 or HA22) in Patients With Hairy Cell Leukemia
Phase I Trial of Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox (CAT-8015 or HA22) in Patients With Hairy Cell Leukemia
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DOI：
10.1200/jco.2011.38.1756
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发表时间：
2012-05-20
影响因子：
45.3
通讯作者：
Pastan, Ira
中科院分区：
文献类型：
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作者：
Kreitman, Robert J.;Tallman, Martin S.;Pastan, Ira
PurposeTo进行一项I期剂量递增试验，评估重组免疫毒素moxetumomab pasudotox（CAT-8015，HA 22）在化疗耐药毛细胞白血病（HCL）中的安全性和反应。患者和方法符合条件的患者在>= 2次既往治疗后复发/难治性HCL，由于血细胞计数异常而需要治疗。患者每隔一天接受莫昔单抗pasudotox 5至50 μ g/kg，共三次剂量（QOD x3），如果患者没有经历疾病进展或产生中和抗体，则以>= 4周的间隔重复多达16个周期。12名患者50 μ g/kg QOD x3，各1 - 16个周期（中位数，4个周期）。未观察到剂量限制性毒性。2例患者出现一过性实验室异常，符合2级溶血性尿毒综合征，肌酐峰值为1.53 - 1.66 mg/dL，血小板最低值为106，000 - 120，000/mu L。28例患者中25%-64%的药物相关毒性包括（频率递减）1 - 2级低白蛋白血症、转氨酶升高、水肿、头痛、低血压、恶心和疲乏。在26例可评价免疫原性的患者中，10例患者（38%）产生的抗体中和了1，000 ng/mL免疫毒素75%以上的细胞毒性，但第1周期后这种免疫原性很罕见（5%）。总体缓解率为86%，在所有剂量水平均观察到缓解，13例患者（46%）达到完全缓解（CR）。只有1 CR持续不到1年，中位无病生存时间尚未达到在26 months.ConclusionMoxetumomab pasudotox在剂量高达50 μ g/kg QOD x3复发/难治性HCL的活动，并有一个安全的配置文件，支持进一步的临床开发治疗这种疾病。J Clin Oncol 30：1822-1828. (c)2012年美国临床肿瘤学会
PurposeTo conduct a phase I dose-escalation trial assessing safety and response of recombinant immunotoxin moxetumomab pasudotox (CAT-8015, HA22) in chemotherapy-resistant hairy cell leukemia (HCL).Patients and MethodsEligible patients had relapsed/refractory HCL after >= two prior therapies and required treatment because of abnormal blood counts. Patients received moxetumomab pasudotox 5 to 50 mu g/kg every other day for three doses (QOD x3), with up to 16 cycles repeating at >= 4-week intervals if patients did not experience disease progression or develop neutralizing antibodies.ResultsTwenty-eight patients were enrolled, including three patients each at 5, 10, 20, and 30 mu g/kg, four patients at 40 mu g/kg, and 12 patients at 50 mu g/kg QOD x3 for one to 16 cycles each (median, four cycles). Dose-limiting toxicity was not observed. Two patients had transient laboratory abnormalities consistent with grade 2 hemolytic uremic syndrome with peak creatinine of 1.53 to 1.66 mg/dL and platelet nadir of 106,000 to 120,000/mu L. Drug-related toxicities in 25% to 64% of the 28 patients included (in decreasing frequency) grade 1 to 2 hypoalbuminemia, aminotransferase elevations, edema, headache, hypotension, nausea, and fatigue. Of 26 patients evaluable for immunogenicity, 10 patients (38%) made antibodies neutralizing more than 75% of the cytotoxicity of 1,000 ng/mL of immunotoxin, but this immunogenicity was rare (5%) after cycle 1. The overall response rate was 86%, with responses observed at all dose levels, and 13 patients (46%) achieved complete remission (CR). Only 1 CR lasted less than 1 year, with the median disease-free survival time not yet reached at 26 months.ConclusionMoxetumomab pasudotox at doses up to 50 mu g/kg QOD x3 has activity in relapsed/refractory HCL and has a safety profile that supports further clinical development for treatment of this disease. J Clin Oncol 30:1822-1828. (c) 2012 by American Society of Clinical Oncology