title: A Phase I Clinical Trial of CHT-25 a 131I-Labeled Chimeric Anti-CD25 Antibody Showing Efficacy in Patients with Refractory Lymphoma.
abstract: 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 ((131)I) 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 (18)F-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 (131)I 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).
authors.affiliation: Authors' Affiliations: Cancer Research UK Targeting and Imaging Group, Department of Oncology, University College London Cancer Institute and Department of Histopathology, University College London Hospitals, London, United Kingdom; Departments of Nuclear Medicine and Radiology, Immunology, and Hematology, Royal Free Hospital, Hampstead, United Kingdom; Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, London, United Kingdom; Drug Development Office, Cancer Research UK, London, United Kingdom.
authors.forename: Gairin
authors.initials: G
authors.lastname: Dancey
authors.forename: John
authors.initials: J
authors.lastname: Violet
authors.forename: Alessandra
authors.initials: A
authors.lastname: Malaroda
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Green
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Roslyn
authors.initials: R
authors.lastname: Francis
authors.forename: Shokri
authors.initials: S
authors.lastname: Othman
authors.forename: Sweta
authors.initials: S
authors.lastname: Parker
authors.forename: John
authors.initials: J
authors.lastname: Buscombe
authors.forename: Natalie
authors.initials: N
authors.lastname: Griffin
authors.forename: Pei-San
authors.initials: PS
authors.lastname: Chan
authors.forename: Anmol
authors.initials: A
authors.lastname: Malhotra
authors.forename: Nicholas
authors.initials: N
authors.lastname: Woodward
authors.forename: Alan
authors.initials: A
authors.lastname: Ramsay
authors.forename: Philip
authors.initials: P
authors.lastname: Ross
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Peter
authors.initials: P
authors.lastname: Amlot
authors.forename: Richard
authors.initials: R
authors.lastname: Begent
authors.forename: Christopher
authors.initials: C
authors.lastname: McNamara