A Phase III Study of Daunorubicin and Cytarabine +/- G3139 (Genasense, Oblimersen Sodium, NSC #683428, IND #58842), a BCL2 Antisense Oligodeoxynucleotide, in Previously Untreated Patients With Acute Myeloid Leukemia (AML) > / = 60 Years

Trial Information

A Phase III Study of Daunorubicin and Cytarabine +/- G3139 (Genasense, Oblimersen Sodium, NSC #683428, IND #58842), a BCL2 Antisense Oligodeoxynucleotide, in Previously Untreated Patients With Acute Myeloid Leukemia (AML) > / = 60 Years

OBJECTIVES: Primary

I. Compare outcome, in terms of overall survival, disease-free survival, event-free
survival, and complete response rate, in older patients with previously untreated acute
myeloid leukemia treated with daunorubicin and cytarabine with or without oblimersen.

Secondary I. Determine the significance of expression of select Bcl-2 family member proteins
known to be modulated by oblimersen (e.g., Bcl-2) or which potentially mediate resistance to
oblimersen (e.g., Bcl-XL or Mcl-1) in predicting clinical outcomes in patients treated with
these regimens.

II. Correlate clinical outcomes with serial changes in levels of mRNA and protein expression
of Bcl-2, its pro-apoptotic binding partner Bax, and other anti-apoptotic Bax-binding
proteins (e.g., Bcl-XL or Mcl-1) in patients treated with these regimens.

III. Determine the effect of pre-treatment characteristics (e.g., morphology, cytogenetics,
molecular features, expression of multidrug resistance molecules, functional assays of drug
efflux, prior myelodysplastic syndromes, age, and white blood cells) on toxicity of these
regimens and outcomes in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2
treatment arms.

Arm I:

Remission induction therapy: Patients receive oblimersen IV continuously on days 1-10,
cytarabine IV continuously on days 4-10, and daunorubicin IV on days 4-6.

Patients who achieve complete remission (CR) proceed to consolidation therapy. Patients who
do not achieve CR receive a second course of induction therapy.

Second remission induction therapy: Patients receive oblimersen IV continuously on days 1-8,
cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.

Patients who achieve CR proceed to consolidation therapy.

Consolidation therapy: Patients receive oblimersen IV continuously on days 1-8 and high-dose
cytarabine IV over 3 hours on days 4-8. Patients with a continuing CR receive a second
course of consolidation therapy.

Arm II:

Remission induction therapy: Patients receive cytarabine IV continuously on days 1-7 and
daunorubicin IV on days 1-3.

Patients who achieve CR proceed to consolidation therapy. Patients who do not achieve CR
receive a second course of induction therapy.

Second remission induction therapy: Patients receive cytarabine IV continuously on days 1-5
and daunorubicin IV on days 1 and 2.

Patients who achieve CR proceed to consolidation therapy.

Consolidation therapy: Patients receive high-dose cytarabine IV over 3 hours on days 1-5.
Patients with a continuing CR receive a second course of consolidation therapy.

In both arms, treatment continues in the absence of disease progression, unacceptable
toxicity, failure to achieve CR after 2 courses of remission induction therapy, the presence
of leukemic cells in the cerebrospinal fluid, leukemic regrowth, or relapse during
consolidation therapy.

Patients are followed every 2 months for 2 years, every 3 months for 2 years, and then
annually for 10 years.

PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this
study within 4.2 years.