title: Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma.
abstract: Lymphoma cells are subject to higher levels of oxidative stress compared with their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase 2 study of imexon (Amplimexon/NSC-714597), a prooxidant molecule, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Imexon was administered at 1000 mg/m(2) IV daily for 5 days in 21-day cycles. Gene expression analysis performed on pretreatment tumor specimens included 13 transcripts used to generate a redox signature score, previously demonstrated to correlate with lymphoma prognosis. Twenty-two patients were enrolled having follicular (n = 9), diffuse large B-cell (DLBCL) (n = 5), mantle cell (n = 3), transformed follicular (n = 2), small lymphocytic (n = 2), and Burkitt (n = 1) lymphoma. The most common grade 3/4 adverse events were anemia (14%) and neutropenia (9%). The overall response rate was 30%, including responses in follicular lymphoma (4 of 9) and DLBCL (2 of 5). Gene expression analyses revealed CD68 and the redox-related genes, GPX1 and SOD2, as well as a higher redox score to correlate with clinical responses. Therefore, pretreatment markers of oxidative stress may identify patients likely to respond to this therapeutic approach. This trial was registered at www.clinicaltrials.gov as #NCT01314014.
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Paul M
authors.initials: PM
authors.lastname: Barr
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Miller
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Derick R
authors.initials: DR
authors.lastname: Peterson
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Baran
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Megan
authors.initials: M
authors.lastname: Herr
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ;
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Spier
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cui
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Roe
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Persky
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Carla
authors.initials: C
authors.lastname: Casulo
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Jamie
authors.initials: J
authors.lastname: Littleton
authors.affiliation: HTG Molecular Diagnostics, Inc., Tucson, AZ; and.
authors.forename: Mark
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Soham
authors.initials: S
authors.lastname: Puvvada
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Terry H
authors.initials: TH
authors.lastname: Landowski
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ;
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dorr
authors.affiliation: Fox Chase Cancer Center, Temple University, Philadelphia, PA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.affiliation: University of Rochester, Wilmot Cancer Center, Rochester, NY;
authors.forename: Steven H
authors.initials: SH
authors.lastname: Bernstein
authors.affiliation: Department of Pathology, University of Arizona, Tucson, AZ;
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Briehl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D006588:Hexanones / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016877:Oxidants / Q000008:administration & dosage* / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D012008:Recurrence; D013482:Superoxide Dismutase / Q000096:biosynthesis; D015996:Survival Rate; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
chemical_list: D014408:Biomarkers, Tumor; D005979:Glutathione Peroxidase; D006588:Hexanones; D009363:Neoplasm Proteins; D016877:Oxidants; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one; C000722067:GPX1 protein, human