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


  • Maria R. Baer's Current address: University of Maryland Greenbaum Cancer Center, Baltimore, Maryland.

  • We thank Eli Estey for providing the statistical design and analysis of the MD Anderson database, Robert Hills for analysis of the United Kingdom MRC database to determine the expected CR rates for a subsequent course of treatment for patients refractory to a single induction course vs. those relapsing in 12 months or less, and Birgitte Roland, University of Calgary and Calgary Laboratory Services, Calgary, Alberta Canada, for performing the karyotype classification.



The p53 antisense oligonucleotide cenersen has been shown to sensitize acute myeloid leukemia (AML) stem cells to DNA damaging agents.


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.


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.


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. Cancer 2011;. © 2011 American Cancer Society.