Acute Myeloid Leukemia Clinical Trial
Arsenic Trioxide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia
Summary
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, cytarabine, and idarubicin, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with cytarabine and idarubicin in treating patients with acute myeloid leukemia.
Full Description
OBJECTIVES:
Determine the maximum tolerated dose and/or biologically effective dose of arsenic trioxide followed by high-dose cytarabine and idarubicin in patients with previously untreated de novo or secondary acute myeloid leukemia.
OUTLINE: This is a dose-escalation study of arsenic trioxide. Patients are stratified according to timing of accrual (before November 2002 vs since November 2002).
Patients receive arsenic trioxide IV over 1 hour on day 1 followed by high-dose cytarabine IV over 1 hour every 12 hours on days 1-6 and idarubicin IV over 30 minutes on days 2-4 (immediately after doses 3, 5 and 7 of cytarabine). Patients also receive filgrastim (G-CSF) subcutaneously beginning 12 hours after the last dose of chemotherapy and continuing until blood counts recover.
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD), current dose used for myelodysplastic syndromes or acute promyelocytic leukemia, or biologically effective dose is reached. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. The biologically effective dose is defined as the dose at which 3 patients with constitutive STAT3 activity have the activity negated after the first dose of arsenic trioxide.
PROJECTED ACCRUAL: A maximum of 40 patients (6 for stratum I [accrued before November 2002] and 34 for stratum II [accrued since November 2002] will be accrued for this study within 3 years.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed de novo or secondary acute myeloid leukemia with ≥ 20% blasts AND at least 1 of the following characteristics*:
Auer rods
Peroxidase or sudan black positive blasts
Chloroacetate esterase-positive or diffusely non-specific esterase-positive blasts
Presence of a myeloid immunophenotype by multiparameter flow cytometry, including expression of one or more myeloid markers (CD13, CD33) on blasts NOTE: *Megakaryocytic leukemia can be diagnosed by the detection of platelet antigens (e.g. factor VIII, glycoprotein Ib or IIb/IIIa) using monoclonal antibodies or the presence of ultrastructural platelet peroxidase
No acute promyelocytic leukemia
No Philadelphia-chromosome positive chronic myeloid leukemia
Prior hematologic disorders, including myelodysplastic syndromes, aplastic anemia, paroxysmal nocturnal hemoglobinuria, and myeloproliferative disorders allowed
PATIENT CHARACTERISTICS:
Age
18 to 59
Performance status
Not specified
Life expectancy
More than 4 weeks
Hematopoietic
Not specified
Hepatic
Bilirubin ≤ 2 times normal*
SGOT ≤ 2 times normal*
Alkaline phosphatase ≤ 2 times normal* NOTE: *Unless abnormalities are directly attributable to leukemia
Renal
Creatinine ≤ 1.5 times normal* NOTE: *Unless abnormalities are directly attributable to leukemia
Cardiovascular
Cardiac ejection fraction ≥ 45%*
Absolute QT interval ≤ 460 msec with potassium > 4.0 mEq/L and magnesium > 1.8 mg/dL
No myocardial infarction within the past 6 months
No uncontrolled symptomatic congestive heart failure
No angina pectoris
No multifocal cardiac arrythmias
No other severe cardiovascular disease NOTE: *Unless abnormalities are directly attributable to leukemia
Other
No serious medical or psychiatric illness that would preclude informed consent or limit survival to < 4 weeks
No uncontrolled diabetes mellitus
No other concurrent active malignancy
No known hypersensitivity to E. coli-derived drug preparations
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
Not specified
Chemotherapy
No prior chemotherapy for acute leukemia, except hydroxyurea to control white blood cell counts
Prior chemotherapy for an antecedent malignancy or other medical condition allowed
Endocrine therapy
Not specified
Radiotherapy
Prior radiotherapy for an antecedent malignancy or other medical condition allowed
Surgery
Not specified
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There is 1 Location for this study
Buffalo New York, 14263, United States
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