Arsenic Trioxide in Treating Young Patients With Refractory Leukemia or Lymphoma
Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide in treating young patients with leukemia or lymphoma.
Description
OBJECTIVES:
- Determine the toxic effects of arsenic trioxide in pediatric patients with refractory leukemia or lymphoma.
- Determine the maximum tolerated dose of this drug in this patient population.
- Determine the plasma pharmacokinetics of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease (acute promyelocytic leukemia [APL] vs non-APL).
- Stratum I (APL patients): Patients receive standard-dose arsenic trioxide IV over 2 hours daily 5 days a week for 4 weeks. Treatment continues every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.
- Stratum II (Non-APL patients): Cohorts of 3-6 patients receive escalating doses of arsenic trioxide (according to the stratum 1 schedule above) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with arsenic trioxide at the recommended phase II dose.
Leukemia patients in both strata without progressive disease who have not achieved complete remission after the first 20 doses may continue to receive arsenic trioxide for 2 additional weeks.
Patients are followed every 3 months for 1 year.
PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for stratum I of this study within 2-3 years. A total of 3-30 patients will be accrued for stratum II of this study within 1-2 years.
Study Design
Primary Purpose: Treatment
Conditions
Leukemia
Intervention
arsenic trioxide
Location
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock
Arkansas
United States
72205
Status
Completed
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00020111
- Information obtained from ClinicalTrials.gov on July 15, 2010
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.
Clinical Trials
Arsenic Trioxide in Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Additional active agents are needed to further improve the treatment of patients with CLL/SLL. Increasing information exists regarding the activity of arsenic trioxide in other hematologic...
A Phase II Study of Gleevec and Arsenic Trioxide in Patients With CML Who Fail Gleevec
1.0 OBJECTIVES 1.1 To test the activity of arsenic trioxide in combination with imatinib in patients with CML with cytogenetic evidence of residual disease. 1.2 To determine the toxicity...
RATIONALE: Tretinoin may help cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as arsenic trioxide and idarubicin, work in d...
RATIONALE: Studying bone marrow and blood samples from patients with leukemia or lymphoma treated with arsenic trioxide may help doctors learn more about cancer. PURPOSE: This research st...
The primary objective of this study is to determine whether low-dose cytarabine in combination with arsenic trioxide is more effective than low-dose cytarabine alone in achieving complete...
PubMed Articles
ABSTRACT The efficacy of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL) is widely accepted. It is necessary to determine the concentration of arsenic since it is a poiso...
Abstract Arsenic trioxide, believed to be a carcinogen and a teratogen, has found its niche in the treatment of Acute Promyelocytic Leukaemia (APL). APL is a disease affecting young patients. Post tre...
ABSTRACT: BACKGROUND: Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce rem...
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...
PURPOSE The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high...
