A Phase I Clinical Trial of CHT-25 a I-131-Labeled Chimeric Anti-CD25 Antibody Showing Efficacy in Patients with Refractory Lymphoma

作者：Dancey Gairin; Violet John; Malaroda Alessandra; Green Alan J; Sharma Surinder K; Francis Roslyn; Othman Shokri; Parker Sweta; Buscombe John; Griffin Natalie; Chan Pei San; Malhotra Anmol; Woodward Nicholas; Ramsay Alan; Ross Philip; Lister T Andrew; Amlot Peter; Begent Richard^*; McNamara Christopher

来源：Clinical Cancer Research, 2009, 15(24): 7701-7710.

DOI：10.1158/1078-0432.CCR-09-1421

Purpose: There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the alpha-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 (I-131) in patients with refractory CD25-positive lymphomas.
Experimental Design: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by F-18-fluorodeoxyglucose positron emission tomography.
Results: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m(2), the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m(2) developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of I-131 and no excessive retention in normal organs. Of nine patients receiving >= 1,200 MBq/m(2), six responded (three complete response and three partial response); one of six patients with administered radioactivity of <= 740 MBq/m(2) had a complete response.
Conclusions: CHT-25 is well tolerated with 1,200 MBq/m(2) administered radioactivity and shows clinical activity in patients who are refractory to conventional therapies. Phase II studies are justified to determine efficacy and toxicity in a broader range of clinical scenarios. (Clin Cancer Res 2009;15(24):7701-10)

• 出版日期2009-12-15