Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes
Summary
RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with arsenic trioxide and to see how well they work in treating patients with myelodysplastic syndromes.
Description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of azacitidine when given in combination with arsenic trioxide in patients with myelodysplastic syndromes (MDS). (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase I)
- Determine the major hematologic response (erythroid response) rate in patients with transfusion-dependent lower-risk MDS treated with this regimen. (Phase II)
- Determine complete and partial remission rates in patients with higher-risk MDS treated with this regimen. (Phase II)
- Determine the toxicity profile of this regimen in these patients. (Phase I)
Secondary
- Determine time to disease progression in patients treated with this regimen. (Phase I and II)
- Determine the overall and progression-free survival of patients treated with this regimen. (Phase I and II)
OUTLINE: This is an multicenter, open-label, phase I, dose escalation study of azacitidine followed by a phase II study. Patients enrolled in the phase II portion are stratified according to baseline International Scoring System score (lower-risk myelodysplastic syndromes [MDS] vs higher-risk MDS).
- Phase I: Patients receive azacitidine subcutaneously once daily on days 1-5 and arsenic trioxide IV over 1-4 hours on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease may receive up to 8 courses of therapy. Patients with responding disease may continue to receive study therapy until a major response or a complete remission is achieved.
Cohorts of 3-6 patients receive escalating doses of azacitidine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive arsenic trioxide as in phase I and azacitidine as in phase I at one dose level below the MTD determined in phase I.
After the completion of study treatment, patients are followed at 4 weeks and then every 3-12 months for survival.
PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 60 patients (30 per stratum) will be accrued for the phase II portion of this study.
Study Design
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Leukemia
Intervention
arsenic trioxide, azacitidine
Location
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles
California
United States
90095-1781
Status
Terminated
Source
Jonsson Comprehensive Cancer Center
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00234000
- Information obtained from ClinicalTrials.gov on August 30, 2012
Medical and Biotech [MESH] Definitions
Arsenic
A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed)
Abelson Murine Leukemia Virus
A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.
Friend Murine Leukemia Virus
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
Arsenic Poisoning
Disorders associated with acute or chronic exposure to compounds containing ARSENIC (ARSENICALS) which may be fatal. Acute oral ingestion is associated with gastrointestinal symptoms and an encephalopathy which may manifest as SEIZURES, mental status changes, and COMA. Chronic exposure is associated with mucosal irritation, desquamating rash, myalgias, peripheral neuropathy, and white transverse (Mees) lines in the fingernails. (Adams et al., Principles of Neurology, 6th ed, p1212)
Moloney Murine Leukemia Virus
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.
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PubMed Articles
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Inorganic arsenic is a common environmental contaminant; chronic exposure to arsenic can alter the physiology of various key immune cells, particularly macrophages. The aim of this research is to eluc...
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