This randomized phase Ib/II trial studies the best dose and side effects of digoxin and how well it works when given together with decitabine in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly diagnosed, has come back, or does not respond to treatment. Drugs used in chemotherapy, such as digoxin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Decitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Given digoxin and decitabine may work better in treating patients with acute myeloid leukemia or myelodysplastic syndrome.
Additional locations may be listed on ClinicalTrials.gov for NCT03113071.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To assess the maximum tolerated dose (MTD) of digoxin when added to a standard dose of decitabine in patients newly diagnosed acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) or those with relapsed/refractory AML/MDS considered unfit for induction chemotherapy.
II. To assess the safety and efficacy of digoxin when added to a standard dose of decitabine in patients newly diagnosed AML/MDS or those with relapsed/refractory AML/MDS considered unfit for induction chemotherapy.
SECONDARY OBJECTIVES:
I. To determine the in vivo epigenetic effect of digoxin in AML and MDS by assessing overall genome methylation (based on LINE-1 global methylation).
II. To determine gene-specific methylation and expression of tumor suppressor genes normally hypermethylated in myeloid leukemia (p15, p21, RIL).
EXPLORATORY OBJECTIVES:
I. To carry out in-depth epigenetic and gene expression analysis to generate preliminary data on profiles that may predict response to study regimen.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive decitabine IV over 1 hour on days 6-10 for course 1. Beginning course 2, patients receive digoxin orally (PO) twice daily (BID) on day 1 and once daily (QD) on days 2-10 and decitabine intravenously (IV) over 1 hour on days 6-10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive digoxin PO BID on day 1 and QD on days 2-10 and decitabine IV over 1 hour on days 6-10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days then every 6 months.
Lead OrganizationFox Chase Cancer Center
Principal InvestigatorPhilip Pancari
