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

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.