This phase I trial studies the side effects and best dose of arsenic trioxide with or without ascorbic acid in treating patients with myelofibrosis. Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving arsenic acid together with ascorbic acid may kill more cancer cells.
Name: Arsenic Trioxide
Name: Ascorbic Acid
Name: Laboratory Biomarker Analysis
Name: Pharmacological Study
Description: The frequency of toxicities will be tabulated by grade across all dose levels and courses. The frequency of toxicities will also be tabulated for the dose chosen as the MTD.
Measure: Adverse events, and their attribution throughout the study Time: Up to 30 days post-treatmentDescription: DLT is defined as any non-hematologic treatment-emergent grade 3 or greater adverse event deemed possibly, probably, or definitely related to the study drug. Exceptions are grade 3 nausea or vomiting, unless in the setting of maximal antiemetic treatment. Hematologic toxicities are not included in the definition of a DLT. The frequency of toxicities will be tabulated by grade across all dose levels and cycles.
Measure: Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 (Stage 1) Time: At 28 daysDescription: The frequency of toxicities will be tabulated by grade across all dose levels and cycles. The frequency of toxicities will also be tabulated for the dose chosen as the MTD.
Measure: Maximum tolerated dose (MTD), defined as the dose level at which 0 or 1 of 6 subjects experience DLT, and 2 of 3 or 2 of 6 experience DLT at the next higher dose level, assessed by the NCI CTC version 3.0 (Stage 1) Time: At 28 daysDescription: Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.
Measure: Change in plasma levels of chemokines as measured by ELISA (Stage 2) Time: Baseline to 24 weeksDescription: Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.
Measure: Change in plasma levels of cytokines as measured by ELISA (Stage 2) Time: Baseline to 24 weeksDescription: Including: soluble vascular cell adhesion molecule 1 (sVCAM-1), neutrophil elastase (NE), matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), stromal cell derived growth factor-1 (SDF-1), TGF-B, and VEGF.
Measure: Change in plasma levels of proteases as measured by enzyme-linked immunosorbent assay (ELISA) (Stage 2) Time: Baseline to 24 weeksAllocation: N/A
Single Group Assignment
There is one SNP
To estimate the efficacy of arsenic trioxide with ascorbic acid in subjects with myelofibrosis, as determined by a reduction in Janus kinase 2 (JAK2) V617F, JAK22T875N, and mutations of the thrombopoietin receptor (MPL515L/K) allele frequency in peripheral blood neutrophils. --- V617F ---