التفاصيل البيبلوغرافية
| العنوان: |
Phase I study of the anti-CD40 humanized monoclonal antibody lucatumumab (HCD122) in relapsed chronic lymphocytic leukemia. |
| المؤلفون: |
Byrd, John C., Kipps, Thomas J., Flinn, Ian W., Cooper, Maureen, Odenike, Olatoyosi, Bendiske, Jennifer, Rediske, John, Bilic, Sanela, Dey, Jyotirmoy, Baeck, Johan, O'Brien, Susan |
| المصدر: |
Leukemia & Lymphoma; Nov2012, Vol. 53 Issue 11, p2136-2142, 7p |
| مصطلحات موضوعية: |
LYMPHOCYTIC leukemia, MONOCLONAL antibody probes, DISEASE relapse, PHARMACOKINETICS, DRUG tolerance, LEUKEMIA treatment |
| مستخلص: |
Lucatumumab is a fully humanized anti-CD40 antibody that blocks interaction of CD40L with CD40 and also mediates antibody-dependent cell-mediated cytotoxicity (ADCC). We evaluated lucatumumab in a phase I clinical trial in chronic lymphocytic leukemia (CLL). Twenty-six patients with relapsed CLL were enrolled on five different dose cohorts administered weekly for 4 weeks. The maximally tolerated dose (MTD) of lucatumumab was 3.0 mg/kg. Four patients at doses of 4.5 mg/kg and 6.0 mg/kg experienced grade 3 or 4 asymptomatic elevated amylase and lipase levels. Of the 26 patients enrolled, 17 patients had stable disease (mean duration of 76 days, range 29-504 days) and one patient had a nodular partial response for 230 days. Saturation of CD40 receptor on CLL cells was uniform at all doses post-treatment but also persisted at trough time points in the 3.0 mg/kg or greater cohorts. At the MTD, the median half-life of lucatumumab was 50 h following the first infusion, and 124 h following the fourth infusion. In summary, lucatumumab had acceptable tolerability, pharmacokinetics that supported chronic dosing and pharmacodynamic target antagonism at doses of 3.0 mg/kg, but demonstrated minimal single-agent activity. Future efforts with lucatumumab in CLL should focus on combination-based therapy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
