• 1-year overall survival rate in older patients with FLT3-ITD acute myeloid leukemia [ Designated as safety issue: No ]
  

• Complete remission rate [ Designated as safety issue: No ]
  
• Overall survival, event-free survival, and remission duration [ Designated as safety issue: No ]
  
• Frequency and severity of adverse events [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• To determine whether 1-year overall survival of older patients with FLT3-ITD acute myeloid leukemia (AML) treated with sorafenib tosylate with induction and post-remission chemotherapy is significantly higher than the historical 1-year survival of similar patients who were not treated with sorafenib tosylate.

Secondary

• To determine the rates of complete remission (CR), CR with incomplete count recovery (CRi), and cytogenetic complete remission (CCyR) to induction chemotherapy in patients treated on this study.
• To determine the overall survival, event-free survival, and remission duration in patients treated on this study.
• To describe the frequency and severity of adverse events of these regimens in patients treated on this study.
• To describe the interaction of pre-treatment disease and patient characteristics including morphology, cytogenetics, immunophenotype, molecular genetic features, WBC count and hemogram, and performance status on clinical outcomes.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive daunorubicin hydrochloride IV on days 1-3, cytarabine IV continuously on days 1-7, and oral sorafenib tosylate twice daily on days 1-7. Patients then undergo a bone marrow aspirate or biopsy on day 14.

  • Patients with persistent disease undergo a second remission induction therapy comprising daunorubicin hydrochloride IV on days 1-2, cytarabine IV continuously on days 1-5, and oral sorafenib tosylate twice daily on days 1-7.
  • Patients who achieve complete response (CR)* proceed to consolidation therapy.
• Consolidation therapy: Patients** receive cytarabine IV over 3 hours on days 1-5 and oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with continued CR proceed to maintenance therapy.
• Maintenance therapy: Patients receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
• NOTE: *Patients who achieve CR and who are eligible for hematopoietic stem cell transplantation (HSCT) are encouraged to enroll in CALGB 100103. Patients in CR who are unable or unwilling to undergo HSCT receive two courses of remission consolidation therapy.
• NOTE: ** Patients in CR/comple remission with incomplete count recovery (CRi) who are unable or unwilling to complete remission consolidation therapy may proceed directly to maintenance therapy after consulting with the CALGB study chair.

Patients may undergo bone marrow aspirate, tumor biopsy, and/or blood sampling at baseline and periodically during study for cytogenetic, biomarker, and mutation analysis.

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