Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Core Binding Factor Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: Cytarabine; Dasatinib; Daunorubicin Hydrochloride; Laboratory Biomarker Analysis
Intervention description: Given IV; Given PO; Given IV; Correlative studies
Intervention MeSH terms: Cytarabine; Daunorubicin; Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well giving combination chemotherapy
      together with dasatinib works in treating patients with newly diagnosed 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. Dasatinib may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving
      combination chemotherapy together with dasatinib may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documentation of disease as assessed by the Alliance reference laboratory at the Ohio
             State University per Cancer and Leukemia Group B (CALGB) 20202, molecular diagnosis of
             core-binding factor (CBF) acute myeloid leukemia (AML) by reverse transcriptase
             polymerase chain reaction (RT-PCR) positive for RUNX1-RUNX1T1 fusion transcript
             resulting from t(8;21)(q22;q22) (or a variant form) or CBFB-MYH11 fusion transcript
             resulting from inv(16)(p13.1q22) or t(16;16)(p13.1;q22) (any % bone marrow or blood
             blasts render the diagnosis of CBF AML based on the World Health Organization [WHO]
             classification)

          -  No prior chemotherapy for leukemia or myelodysplasia with the following exceptions:

               -  Emergency leukapheresis

               -  Emergency treatment for hyperleukocytosis with hydroxyurea,

               -  Cranial radiotherapy (RT) for central nervous system (CNS) leukostasis (one dose
                  only),

               -  Growth factor/cytokine support/non-cytotoxic molecular-targeted agents

          -  AML patients with a history of antecedent myelodysplasia (MDS) remain eligible for
             treatment on this trial

          -  Patients who have developed therapy related myeloid neoplasm (t-MN) after prior
             radiation therapy or chemotherapy for another cancer or disorder are eligible

          -  Left ventricular ejection fraction >= lower limit of institutional normal by
             multigated acquisition (MUGA) or echocardiogram (ECHO) scan

          -  Patients must not have had myocardial infarction within 6 months of registration

          -  Patients must not have had ventricular tachyarrhythmia within 6 months of registration

          -  Patients must have no major conduction abnormality (unless a cardiac pacemaker is
             present)

          -  Bilirubin must not be < 2.5 times upper limit of normal

          -  Patients must be non-pregnant and non-nursing; pregnant or nursing patients may not be
             enrolled; women of childbearing potential (WOCBP) must have a negative serum or urine
             pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to
             registration; women of child-bearing potential must either commit to continued
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control - one highly effective method (e.g., intrauterine device [IUD], hormonal,
             tubal ligation, or partner's vasectomy), and one additional effective method (e.g.,
             latex condom, diaphragm, or cervical cap) - AT THE SAME TIME, before she begins
             dasatinib therapy, during treatment and at least 12 weeks after treatment is complete;
             "Women of childbearing potential" is defined as a sexually active mature woman who has
             not undergone a hysterectomy or who has had menses at any time in the preceding 24
             consecutive months

          -  Patients with congenital long QT syndrome or non-congenital corrected QT (QTc)
             prolongation (defined as a QTc interval consistently equal to or greater than 480
             msecs) that cannot be corrected by infusion of electrolytes and/or discontinuation of
             other medications prior to start of treatment are excluded