Myelodysplastic syndromes (MDS) are hematological disorders characterized by ineffective hematopoiesis. DNA hypomethylating agents such as decitabine have been shown to have activity in this disorder by reversing the epigenetic mechanism of gene silencing.~Acute Myeloid Leukemia (AML) is a hematological disorder characterized by ineffective hematopoiesis and malignant expansion of clonal myeloid cells. In elderly patients (≥ 60 years old), MDS commonly precedes the diagnosis of AML. Standard therapy for AML consists of cytotoxic chemotherapy and is often followed with allogeneic stem cell transplantation. Unfortunately, elderly patients are often unable to tolerate such aggressive therapy.~Arsenic has also shown activity in patients with MDS and AML though modulation of apoptosis via increased oxidative stress. In preclinical modes, arsenic activity is related to the production of radical oxygen species that damage mitochondria. Cellular glutathione acts as a cellular antioxidant and can be depleted with the vitamin ascorbic acid which increases intracellular oxidative stress and sensitivity to arsenic trioxide induced apoptosis.~We are studying the combination of decitabine, arsenic trioxide and ascorbic acid, two primary agents and one vitamin all with different mechanisms of action in order to improve the response rate in patients with MDS and AML. This is an open-label, single-arm, single-center, dose escalation Phase I trial of decitabine, arsenic trioxide and ascorbic acid in patients with MDS, either de novo or secondary, fitting any of the FAB classifications and AML.
This study is designed to test the combination of decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia