Trial Information

Phase II Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy Plus Dasatinib (NSC #732517, IND #73969) and Continuation Therapy With Dasatinib Alone in Newly Diagnosed Patients With Core Binding Factor Acute Myeloid Leukemia (AML)

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of dasatinib with intensive induction therapy
(daunorubicin hydrochloride and cytarabine), consolidation chemotherapy (high-dose
cytarabine), and as single agent in maintenance therapy in patients with newly diagnosed
core-binding factor acute myeloid leukemia (AML).

SECONDARY OBJECTIVES:

I. To assess clinical outcomes such as event-free survival (EFS), complete response rate
(CR), cumulative incidence of relapse (CIR), cumulative incidence of death (CID),
disease-free survival (DFS), and overall survival (OS) of patients treated with these
regimens.

II. To describe the frequency and severity of adverse events of patients treated on this
study during induction, consolidation, and continuation therapy.

III. To describe the interaction of pretreatment disease and patient characteristics
including morphology, cytogenetics, immunophenotype, molecular genetic features, white blood
cell count and hemogram, and performance status on clinical outcomes.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY (course 1): Patients receive daunorubicin hydrochloride IV on days 1-3,
cytarabine IV continuously over 168 hours on days 1-7, and dasatinib orally (PO) once daily
on days 8-21. Patients with responsive disease on day 21 undergo consolidation therapy, and
patients with non-responsive disease on day 21 (bone marrow cellularity ≥ 20 % and leukemia
blasts ≥ 5%) receive a second course of induction therapy.

INDUCTION THERAPY (course 2): Patients receive daunorubicin hydrochloride IV on days 1-3,
cytarabine IV continuously over 120 hours on days 1-5, and dasatinib PO once a day on days
6-19. Patients achieving complete response receive consolidation therapy.

CONSOLIDATION THERAPY: Patients receive high-dose cytarabine IV over 3 hours on days 1, 3,
and 5, and dasatinib PO once daily on days 6-26. Treatment repeats every 28 days for 4
courses in the absence of disease progression or unacceptable toxicity. Patients in complete
remission receive continuation therapy.

CONTINUATION THERAPY: Patients receive dasatinib PO on days 1-28. Treatment repeats every 28
days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 2 months for 2 years,
every 3 months for 2 years, and then every year for a up to 10 years.