Randomized Phase II Study of Epigenetic Priming Using Decitabine With Induction Chemotherapy in Patients With Acute Myelogenous Leukemia (AML)
- To "Pick a Winner" by deciding whether further development of epigenetic priming with
decitabine prior to standard "7+3" induction chemotherapy should be pursued.
- To determine whether epigenetic priming with decitabine prior to standard cytarabine
and daunorubicin hydrochloride "7+3" induction chemotherapy has sufficient efficacy to
warrant further development as assessed by an overall CR1 rate ≥ 50%.
- To establish the safety and expected toxicities of decitabine when used as priming for
cytarabine and daunorubicin hydrochloride "7+3" induction chemotherapy in acute myeloid
- To assess the pharmacodynamics of DNA hypomethylation when decitabine is administered
as a short infusion.
- To investigate, in selected cases, the molecular and cellular consequences of
decitabine-induced hypomethylation by assessing the effects of decitabine-mediated
hypomethylation on transcriptional patterns in AML cells, and by determining the effect
of hypomethylation on the differentiation and/or apoptosis of leukemic blasts.
- To identify biomolecular correlates of treatment response (biomarkers) to induction
chemotherapy in AML based upon the epigenetic pattern of DNA methylation in AML
specimens obtained prior to treatment. (exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to age (< 50 years
vs 50-65 years), white blood cell count (≤ 30 K/mL vs > 30 K/mL), cytogenetic risk group
(intermediate vs adverse risk), and antecedent hematological condition preceding the
diagnosis of acute myeloid leukemia (yes vs no). Patients are randomized to 1 of 2 treatment
- Arm I: Patients receive induction chemotherapy comprising daunorubicin hydrochloride IV
daily on days 1-3 and cytarabine IV continuously on days 1-7 in the absence of disease
progression or unacceptable toxicity. Patients who do not achieve a complete remission
(CR) after the first induction-chemotherapy course receive a second identical induction
- Arm II: Patients receive decitabine IV over 24 hours on days -5 to -1. Patients then
receive induction chemotherapy as in arm I in the absence of disease progression or
unacceptable toxicity. Patients who do not achieve a CR after the first
induction-chemotherapy course receive a second identical induction course.
Patients undergo blood, bone marrow, and oral mucosa cells sample collection at baseline,
prior to induction therapy, and after treatment for DNA methylation studies and
After completion of study treatment, patients are followed up for up to 10 years.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Complete remission rate after one course of induction chemotherapy
Joseph M. Scandura, MD
Weill Medical College of Cornell University
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|New York Weill Cornell Cancer Center at Cornell University||New York, New York 10021|