Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia

Jorge Cortes, Hagop Kantarjian, Edward D. Ball, John DiPersio, Jonathan E. Kolitz, Hugo F. Fernandez, Mark Goodman, Gautam Borthakur, Maria R. Baer, Meir Wetzler

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents. METHODS: To determine whether cenersen merits testing in larger efficacy studies, an exploratory study of cenersen in combination with idarubicin either alone or with 1 of 2 doses of cytarabine was performed in first-salvage AML patients. Patients who either had failed to respond to a single induction course or had responded to induction but relapsed within 12 months were enrolled. Stopping rules based on an expected 14% complete response (CR) rate were applied to each treatment arm. RESULTS: Fifty-three patients were treated, and none of the arms was terminated for lack of activity. Nearly all patients received a single course unless they responded. Ten of the 53 (19%) patients responded (8 CR and 2 CR with incomplete platelet recovery). There was a positive trend for a better response rate with increasing intensity of chemotherapy in the patients refractory to front-line treatment compared with those who had relapsed previously. One-third (17/53) of the patients received cenersen inhibitors (acetaminophen and/or high dose antioxidants) during treatment, and none of these responded to treatment. No unique toxicity was attributed to cenersen. CONCLUSION: The results of this study suggested that the combination of cenersen with chemotherapy may have clinical efficacy, and additional studies are warranted to explore its full potential.

Original languageEnglish (US)
Pages (from-to)418-427
Number of pages10
JournalCancer
Volume118
Issue number2
DOIs
StatePublished - Jan 15 2012
Externally publishedYes

Fingerprint

Idarubicin
Antisense Oligonucleotides
Cytarabine
Acute Myeloid Leukemia
Myeloid Progenitor Cells
Drug Therapy
Therapeutics
Acetaminophen
cenersen
Blood Platelets
Antioxidants
DNA

Keywords

  • Acute myeloid leukemia
  • Antisense
  • Cenersen
  • p53
  • Refractory
  • Relapsed

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia. / Cortes, Jorge; Kantarjian, Hagop; Ball, Edward D.; DiPersio, John; Kolitz, Jonathan E.; Fernandez, Hugo F.; Goodman, Mark; Borthakur, Gautam; Baer, Maria R.; Wetzler, Meir.

In: Cancer, Vol. 118, No. 2, 15.01.2012, p. 418-427.

Research output: Contribution to journalArticle

Cortes, J, Kantarjian, H, Ball, ED, DiPersio, J, Kolitz, JE, Fernandez, HF, Goodman, M, Borthakur, G, Baer, MR & Wetzler, M 2012, 'Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia', Cancer, vol. 118, no. 2, pp. 418-427. https://doi.org/10.1002/cncr.26292
Cortes, Jorge ; Kantarjian, Hagop ; Ball, Edward D. ; DiPersio, John ; Kolitz, Jonathan E. ; Fernandez, Hugo F. ; Goodman, Mark ; Borthakur, Gautam ; Baer, Maria R. ; Wetzler, Meir. / Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia. In: Cancer. 2012 ; Vol. 118, No. 2. pp. 418-427.
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AU - Kolitz, Jonathan E.

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AB - BACKGROUND: The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents. METHODS: To determine whether cenersen merits testing in larger efficacy studies, an exploratory study of cenersen in combination with idarubicin either alone or with 1 of 2 doses of cytarabine was performed in first-salvage AML patients. Patients who either had failed to respond to a single induction course or had responded to induction but relapsed within 12 months were enrolled. Stopping rules based on an expected 14% complete response (CR) rate were applied to each treatment arm. RESULTS: Fifty-three patients were treated, and none of the arms was terminated for lack of activity. Nearly all patients received a single course unless they responded. Ten of the 53 (19%) patients responded (8 CR and 2 CR with incomplete platelet recovery). There was a positive trend for a better response rate with increasing intensity of chemotherapy in the patients refractory to front-line treatment compared with those who had relapsed previously. One-third (17/53) of the patients received cenersen inhibitors (acetaminophen and/or high dose antioxidants) during treatment, and none of these responded to treatment. No unique toxicity was attributed to cenersen. CONCLUSION: The results of this study suggested that the combination of cenersen with chemotherapy may have clinical efficacy, and additional studies are warranted to explore its full potential.

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