A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age
I. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and
oblimersen in older patients with previously untreated acute myeloid leukemia.
II. Determine the qualitative and quantitative toxic effects of this regimen in these
III. Determine the pharmacokinetics of oblimersen in this regimen in these patients.
IV. Determine the disease-free survival and overall survival of patients treated with this
V. Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after
initiation of treatment with oblimersen.
VI. Determine therapeutic response (complete remission) in patients treated with this
OUTLINE: This is a dose-escalation study of daunorubicin. Patients are stratified according
to disease status (primary vs secondary).
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and
cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day
17 or evidence of refractory disease receive a second induction comprising G3139 IV
continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from
induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over
4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner
than 14 days after hematologic recovery from the first course.
Cohorts of 3-6 patients receive escalating doses of daunorubicin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Patients are followed every 2 months for 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of cytarabine and daunorubicin in combination with G3139, defined as the dose level just below the dose level at which DLT is observed in 2 patients, graded according to NCI CTC version 2.0
Up to day 10
Ohio State University
United States: Food and Drug Administration
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