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
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Washington University
St Louis, Missouri, United States
To define the maximum tolerated dose and dose-limiting toxicities during four cycles of combination decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) previously untreated with hypomethylating agents.
Time frame: 4 months after the final patient on the final cohort starts treatment
To estimate the rate of complete remission (CR) and partial remission (PR) after four cycles of therapy in patients with MDS.
Time frame: After 4 cycles of treatment
To determine the rate of hematologic improvement
Time frame: Weekly through the end of treatment
To determine the rate of transfusion independence
Time frame: Through completion of treatment
To determine the time to disease progression to AML
Time frame: Every 4 weeks during treatment and then every 2 months for 2 years after the first dose of study drug
To determine the rate of cytogenetic response
Time frame: After every 2 cycles
To determine the rate of overall survival
Time frame: Every 4 weeks during treatment and then every 2 months for 2 years after the first dose of study drug
To determine changes in bone marrow vascular density
Time frame: At baseline, end of cycle 2, end of cycle 4, and end of study
To determine changes in angiogenic mRNA expression.
Time frame: Baseline, end of cycle 2, end of cycle 4, and end of study
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.