RGD Reference Report - Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma. - Rat Genome Database

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Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma.

Authors: Barr, PM  Miller, TP  Friedberg, JW  Peterson, DR  Baran, AM  Herr, M  Spier, CM  Cui, H  Roe, DJ  Persky, DO  Casulo, C  Littleton, J  Schwartz, M  Puvvada, S  Landowski, TH  Rimsza, LM  Dorr, RT  Fisher, RI  Bernstein, SH  Briehl, MM 
Citation: Barr PM, etal., Blood. 2014 Aug 21;124(8):1259-65. doi: 10.1182/blood-2014-04-570044. Epub 2014 Jul 11.
RGD ID: 11352765
Pubmed: PMID:25016003   (View Abstract at PubMed)
PMCID: PMC4141515   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2014-04-570044   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
non-Hodgkin lymphoma treatmentIDA 11352765 RGD 
non-Hodgkin lymphoma treatmentISOGPX1 (Homo sapiens)11352765; 11352765 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gpx1  (glutathione peroxidase 1)

Genes (Mus musculus)
Gpx1  (glutathione peroxidase 1)

Genes (Homo sapiens)
GPX1  (glutathione peroxidase 1)


Additional Information