Daunorubicin Hydrochloride, Cytarabine, and Nilotinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well daunorubicin hydrochloride, cytarabine, and nilotinib
      work in treating patients newly diagnosed with acute myeloid leukemia. Drugs used in
      chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to
      stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
      or by stopping them from spreading. Nilotinib may stop the growth of cancer cells by blocking
      some of the enzymes needed for cell growth. Giving daunorubicin hydrochloride with cytarabine
      and nilotinib may kill more cancer cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the complete response rates of combination nilotinib, cytarabine, and
      daunorubicin (daunorubicin hydrochloride) in patients newly diagnosed with acute myeloid
      leukemia (AML) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit)
      overexpression.

      SECONDARY OBJECTIVES:

      I. Determine the 2-year overall survival (OS) and disease-free survival (DFS) rates.

      II. Determine the complete response duration in patients treated with this regimen.

      III. Assess the safety and toxicity of this regimen based on National Cancer Institute (NCI)
      Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

      TERTIARY OBJECTIVES:

      I. Assess the prognostic and predictive factors (Kit mutation/expression level, fms-related
      tyrosine kinase 3 [Flt3] mutation) for patients treated with this regimen.

      II. Assess the patterns of molecular response and relapse for Kit. III. Assess the effect on
      minimal residual disease (MRD) by polymerase chain reaction (PCR) or flow cytometry.

      OUTLINE:

      INDUCTION THERAPY: Patients receive daunorubicin hydrochloride intravenously (IV) over 10
      minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib orally (PO) twice
      daily (BID) on days 4-14. Patients achieving complete remission (CR) or complete remission
      with incomplete blood count recovery (CRi) proceed to consolidation therapy. Patients not
      achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery
      receive another course of induction therapy.

      CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and
      nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence
      of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to
      maintenance therapy.

      MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every
      84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for up to 3
      years.
    

Intervention name(s): Cytarabine; Daunorubicin Hydrochloride; Laboratory Biomarker Analysis; Nilotinib; Pharmacological Study
Intervention type(s): Drug; Drug; Other; Drug; Other
Intervention description(s): Given IV; Given IV; Correlative studies; Given PO; Correlative studies
Other intervention name(s): .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosar-U; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; AMN 107; Tasigna
Intervention MeSH terms: Cytarabine; Daunorubicin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment