Phase II study of imexon, a pro-oxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma
Mené sur 22 patients atteints d'un lymphome non hodgkinien B récidivant/réfractaire, cet essai de phase I évalue l'activité antitumorale et la toxicité de l'imexon, une molécule pro-oxydante
Lymphoma cells are subject to higher levels of oxidative stress as compared to their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase II study of imexon (Amplimexon/NSC-714597), a pro-oxidant molecule, in patients with relapsed / refractory B-cell non-Hodgkin lymphomas (NHL). Imexon was administered at 1000 mg/m2 intravenously daily for 5 days in 21-day cycles. Gene expression analysis performed on pre-treatment 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 (4/9) and DLBCL (2/5). 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. To our knowledge, this is the first demonstration of clinical activity with a pro-oxidant molecule in lymphoma. Pre-treatment markers of oxidative stress may identify patients likely to respond to this therapeutic approach. This study was registered at ClinicalTrials.gov as #NCT01314014.