Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

• Survival rate during induction therapy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  

• Absence of pleural or pericardial effusion [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
  The frequency and severity of adverse events for patients treated on this study during induction, consolidation and continuation therapy will be tabulated.
  
  
• Absence of liver toxicity that exceeds grade 2 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
  The frequency and severity of adverse events for patients treated on this study during induction, consolidation and continuation therapy will be tabulated.
  
  
• Rate of early/hypoplastic death [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
  The frequency and severity of adverse events for patients treated on this study during induction, consolidation and continuation therapy will be tabulated.
  
  
• Event-free survival [ Time Frame: From registration to failure to achieve CR, relapse after CR is attained, or death whichever comes first, assessed up to 10 years ] [ Designated as safety issue: No ]
  
• Complete response rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  
• Cumulative incidence of relapse [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  
• Cumulative incidence of death [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  
• Disease-free survival [ Time Frame: From achievement of CR to relapse or death whichever comes first, assessed up to 10 years ] [ Designated as safety issue: No ]
  
• Overall survival [ Time Frame: From registration to death, assessed up to 10 years ] [ Designated as safety issue: No ]
  

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.