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

Paul M. Barr, Thomas P Miller, Jonathan W. Friedberg, Derick R. Peterson, Andrea M. Baran, Megan Herr, Catherine S Perry, Haiyan Cui, Denise Roe, Daniel O. Persky, Carla Casulo, Jamie Littleton, Mark Schwartz, Soham D Puvvada, Terry H Landowski, Lisa M Rimsza, Robert T Dorr, Richard I. Fisher, Steven H. Bernstein, Margaret M Briehl

Research output: Contribution to journalArticle

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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/m2 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 mostcommon 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.

Original languageEnglish (US)
Pages (from-to)1259-1265
Number of pages7
JournalBlood
Volume124
Issue number8
DOIs
StatePublished - Aug 21 2014

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B-Cell Lymphoma
Refractory materials
Non-Hodgkin's Lymphoma
Oxidation-Reduction
Cells
Lymphoma
Molecules
Oxidative stress
Gene expression
Oxidative Stress
B-Lymphocytes
Gene Expression
Follicular Lymphoma
Neutropenia
Anemia
Tumors
Genes
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma. / Barr, Paul M.; Miller, Thomas P; Friedberg, Jonathan W.; Peterson, Derick R.; Baran, Andrea M.; Herr, Megan; Perry, Catherine S; Cui, Haiyan; Roe, Denise; Persky, Daniel O.; Casulo, Carla; Littleton, Jamie; Schwartz, Mark; Puvvada, Soham D; Landowski, Terry H; Rimsza, Lisa M; Dorr, Robert T; Fisher, Richard I.; Bernstein, Steven H.; Briehl, Margaret M.

In: Blood, Vol. 124, No. 8, 21.08.2014, p. 1259-1265.

Research output: Contribution to journalArticle

Barr, PM, Miller, TP, Friedberg, JW, Peterson, DR, Baran, AM, Herr, M, Perry, CS, Cui, H, Roe, D, Persky, DO, Casulo, C, Littleton, J, Schwartz, M, Puvvada, SD, Landowski, TH, Rimsza, LM, Dorr, RT, Fisher, RI, Bernstein, SH & Briehl, MM 2014, 'Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma', Blood, vol. 124, no. 8, pp. 1259-1265. https://doi.org/10.1182/blood-2014-04-570044
Barr, Paul M. ; Miller, Thomas P ; Friedberg, Jonathan W. ; Peterson, Derick R. ; Baran, Andrea M. ; Herr, Megan ; Perry, Catherine S ; Cui, Haiyan ; Roe, Denise ; Persky, Daniel O. ; Casulo, Carla ; Littleton, Jamie ; Schwartz, Mark ; Puvvada, Soham D ; Landowski, Terry H ; Rimsza, Lisa M ; Dorr, Robert T ; Fisher, Richard I. ; Bernstein, Steven H. ; Briehl, Margaret M. / Phase 2 study of imexon, a prooxidant molecule, in relapsed and refractory B-cell non-Hodgkin lymphoma. In: Blood. 2014 ; Vol. 124, No. 8. pp. 1259-1265.
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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/m2 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 mostcommon 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.",
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AU - Barr, Paul M.

AU - Miller, Thomas P

AU - Friedberg, Jonathan W.

AU - Peterson, Derick R.

AU - Baran, Andrea M.

AU - Herr, Megan

AU - Perry, Catherine S

AU - Cui, Haiyan

AU - Roe, Denise

AU - Persky, Daniel O.

AU - Casulo, Carla

AU - Littleton, Jamie

AU - Schwartz, Mark

AU - Puvvada, Soham D

AU - Landowski, Terry H

AU - Rimsza, Lisa M

AU - Dorr, Robert T

AU - Fisher, Richard I.

AU - Bernstein, Steven H.

AU - Briehl, Margaret M

PY - 2014/8/21

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N2 - 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/m2 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 mostcommon 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.

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