title: Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML.
abstract: We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m² for 7 days) and daunorubicin (60 mg/m² × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+) bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876.
authors: Leukemia Program, Weill Cornell Medical College, New York, NY, USA. jms2003@med.cornell.edu
authors: Joseph M
authors: JM
authors: Scandura
authors: Gail J
authors: GJ
authors: Roboz
authors: Michelle
authors: M
authors: Moh
authors: Ewelina
authors: E
authors: Morawa
authors: Fabienne
authors: F
authors: Brenet
authors: J Robi
authors: JR
authors: Bose
authors: Luis
authors: L
authors: Villegas
authors: Usama S
authors: US
authors: Gergis
authors: Sebastian A
authors: SA
authors: Mayer
authors: Cindy M
authors: CM
authors: Ippoliti
authors: Tania J
authors: TJ
authors: Curcio
authors: Ellen K
authors: EK
authors: Ritchie
authors: Eric J
authors: EJ
authors: Feldman
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