Arsenic Trioxide With or Without Tretinoin in Treating Patients With Hematologic Cancer That Has Not Responded to Previous Therapy
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells.
PURPOSE: Phase I/II trial to study the effectiveness of arsenic trioxide with or without tretinoin in treating patients who have hematologic cancer that has not responded to previous therapy.
Description
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose limiting toxicity of arsenic trioxide in patients with refractory hematologic malignancies. II. Determine the complete or partial response to arsenic trioxide at the MTD in these patients. III. Determine the response to and toxicity of arsenic trioxide when administered with tretinoin in these patients. IV. Determine the pharmacokinetics of arsenic trioxide with and without tretinoin in these patients. V. Determine the chronic toxicities of these treatment regimens in these patients.
OUTLINE: This is a dose escalation and efficacy study of arsenic trioxide. In the efficacy study, patients are stratified according to diagnosis (acute myelogenous leukemia vs acute lymphocytic leukemia vs myelodysplastic syndrome vs multiple myeloma vs non-Hodgkin's lymphoma and Hodgkin's disease). Phase I: Patients receive arsenic trioxide IV over 2 hours daily for 28 days. Treatment repeats every 42-59 days in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) or partial remission (PR) receive up to 4 courses. Patients who fail to achieve CR or PR or who experience disease progression may receive arsenic trioxide and tretinoin daily for 28 days every 42-59 days for up to 7 courses. Patients who fail to achieve CR or PR or experience disease progression with arsenic trioxide and tretinoin are removed from study. Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Phase II: Patients receive the MTD of arsenic trioxide as in phase I for up to 7 courses. Patients who fail to achieve CR or PR after 3 courses or experience disease progression are either taken off study or treated with arsenic trioxide and tretinoin as in phase I. Patients are followed monthly for 6 months, and then every 3 months for 18 months.
PROJECTED ACCRUAL: Approximately 63-290 patients (3-40 treated in phase I; 10-155 treated in phase II (10-29 patients per diagnostic group); and 50-95 treated with arsenic trioxide and tretinoin) will be accrued for this study.
Study Design
Primary Purpose: Treatment
Conditions
Leukemia
Intervention
arsenic trioxide, tretinoin
Location
Washington University Barnard Cancer Center
Saint Louis
Missouri
United States
63110
Status
Active, not recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00006220
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:57:25-0400
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Medical and Biotech [MESH] Definitions
Tretinoin
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
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)
