Arsenic Trioxide With or Without Ascorbic Acid in Treating Patients With Myelofibrosis
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|ClinicalTrials.gov Identifier: NCT01014546|
Recruitment Status : Terminated (low accrual)
First Posted : November 17, 2009
Last Update Posted : July 26, 2016
|Condition or disease||Intervention/treatment||Phase|
|Essential Thrombocythemia Polycythemia Vera Primary Myelofibrosis||Drug: Arsenic Trioxide Dietary Supplement: Ascorbic Acid Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
I. To determine the safety and maximum tolerated dose of oral arsenic trioxide with or without ascorbic acid in subjects with myelofibrosis.
I. To estimate the incidence, severity, and attribution of treatment-emergent adverse events.
II. To estimate the rate of complete or major clinical-hematological response from treatment with arsenic trioxide and ascorbic acid in this subject population as measured by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response criteria.
III. To measure arsenic trioxide levels in the plasma of patients treated with and without ascorbic acid on this protocol.
IV. 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.
V. To examine the effect of treatment on biological markers of myeloproliferation, cytokine production and hematopoietic stem cell mobilization. In particular, the following markers of disease will be measured: cluster of differentiation (CD)34+ cell count in peripheral blood measured by cytofluorimetry, plasma vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-B), stromal cell-derived factor-1 (SDF-1), neutrophil elastase levels by commercial assays.
VI. To examine single nucleotide polymorphism (SNP) in the arsenic trioxide pathway in subjects with myelofibrosis treated with arsenic trioxide and ascorbic acid.
OUTLINE: This is a dose-escalation study of arsenic trioxide.
Patients receive arsenic trioxide orally (PO) once daily (QD) in orange juice on days 1-21. Patients may also receive ascorbic acid PO QD on days 1-21. Treatment repeats every 28 days for up to 168 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 4 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Oral Arsenic Trioxide With or Without Ascorbic Acid in Adults With Myelofibrosis|
|Study Start Date :||April 2010|
|Actual Primary Completion Date :||February 2015|
Experimental: Treatment (arsenic trioxide with or without ascorbic acid)
Patients receive arsenic trioxide PO QD in orange juice on days 1-21. Patients may also receive ascorbic acid PO QD on days 1-21. Treatment repeats every 28 days for up to 168 days in the absence of disease progression or unacceptable toxicity.
Drug: Arsenic Trioxide
Dietary Supplement: Ascorbic Acid
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Adverse events, and their attribution throughout the study [ Time Frame: Up to 30 days post-treatment ]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.
- Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 (Stage 1) [ Time Frame: At 28 days ]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.
- 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 Frame: At 28 days ]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.
- Change in absolute number of circulating CD34+ cells in the peripheral blood (Stage 2 only) [ Time Frame: Baseline to 24 weeks ]
- Change in JAK2/MPL (Stage 2 only) [ Time Frame: Baseline to 24 weeks ]
- Change in plasma levels of chemokines as measured by ELISA (Stage 2) [ Time Frame: Baseline to 24 weeks ]Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.
- Change in plasma levels of cytokines as measured by ELISA (Stage 2) [ Time Frame: Baseline to 24 weeks ]Including: sVCAM-1, NE, MMP-2, MMP-9, SDF-1, TGF-B, and VEGF.
- Change in plasma levels of proteases as measured by enzyme-linked immunosorbent assay (ELISA) (Stage 2) [ Time Frame: Baseline to 24 weeks ]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.
- Disease response assessed using the IWG-MRT response criteria [ Time Frame: Up to 24 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01014546
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Eunice Wang, MD||Roswell Park Cancer Institute|