Arsenic Trioxide, High-Dose Cytarabine and Idarubicin Induction Therapy in Previously Untreated de Novo and Secondary Adult Acute Myeloid Leukemia Patients < 60 Years Old - A Phase I Study
18 Years
59 Years
Both
Leukemia
Trial Information
Arsenic Trioxide, High-Dose Cytarabine and Idarubicin Induction Therapy in Previously Untreated de Novo and Secondary Adult Acute Myeloid Leukemia Patients < 60 Years Old - A Phase I Study
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose and/or biologically effective dose or arsenic trioxide
Outcome Time Frame:
30 days after completion of study treatment
Safety Issue:
Yes
Principal Investigator
Meir Wetzler, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000387999
NCT ID:
NCT00093483
Start Date:
April 2002
Completion Date:
December 2009
Related Keywords:
- Leukemia
- adult acute basophilic leukemia
- adult acute eosinophilic leukemia
- adult erythroleukemia (M6a)
- adult pure erythroid leukemia (M6b)
- adult acute megakaryoblastic leukemia (M7)
- adult acute minimally differentiated myeloid leukemia (M0)
- adult acute monoblastic leukemia (M5a)
- adult acute monocytic leukemia (M5b)
- adult acute myeloblastic leukemia with maturation (M2)
- adult acute myeloblastic leukemia without maturation (M1)
- adult acute myelomonocytic leukemia (M4)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- untreated adult acute myeloid leukemia
- secondary acute myeloid leukemia
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
