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
- 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
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and/or biologically effective dose or arsenic trioxide
30 days after completion of study treatment
Meir Wetzler, MD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|