Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Inclusion Criteria:

   - Morphological diagnosis of AML other then acute promyelocytic leukemia (FAB M3)
   according to WHO diagnostic criteria; diagnosis of AML must be based on bone marrow or
   peripheral blood studies obtained within 28 days prior to study registration or start
   of hydroxyurea (for patients presenting with WBC >= 10,000/uL), and no potentially
   anti-leukemic therapy (with the exception of hydroxyurea) must have been given between
   AML diagnosis and study registration; a bone marrow biopsy is not routinely required
   but should be obtained if the aspirate is dilute, hypocellular, or inaspirable;
   outside bone marrows performed within the stipulated time period are acceptable as
   long as the slides are reviewed at a study institution

   - Cytogenetic analysis on bone marrow or peripheral blood specimen is available; based
   on the result from the first interim analysis, patients stratified into the good-risk
   group are only eligible if their AML has favorable cytogenetics (core-binding factor
   AML) or has a normal karyotype; patients stratified into the poor-risk group are
   eligible independent of the cytogenetic analysis

   - Pretreatment bone marrow and peripheral blood specimens for correlative studies are
   available; if bone marrow was performed at an outside facility, submission of
   peripheral blood only is acceptable as long as the peripheral blast count is >
   5,000/uL and > 50% of total WBC

   - Patients with a history of antecedent MDS are eligible, if prior treatment did not
   include intensive chemotherapy; patients may have received hematopoietic growth
   factors, thalidomide/lenalidomide, 5-azacytidine/decitabine, arsenic trioxide, signal
   transduction inhibitors, or low dose cytarabine (< 100 mg/m2/day) for treatment of
   MDS; patients must be off prior therapy for MDS at least 30 days prior to study
   registration, and all non-hematologic toxicities must have resolved to < grade 2

   - ECOG/WHO/Zubrod performance status of 0-3

   - Bilirubin =< 2.5 x Institutional Upper Limit of Normal (IULN) unless elevation is
   thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
   (assessed within 14 days prior to registration)

   - SGOT (AST) and SPGT (ALT) =< 1.5 x IULN unless elevation is thought to be due to
   hepatic infiltration by AML (assessed within 14 days prior to registration)

   - Serum creatinine =< 1.5 x IULN (assessed within 14 days prior to registration)

   - Left ventricular ejection fraction >= 40% and no clinical evidence of congestive heart
   failure (assessed within 28 days prior to registration, e.g. by MUGA scan or
   echocardiography)

   - Men of reproductive potential must use an effective contraceptive method throughout
   the study and for a period of at least 3 months after the study

   - Women must be postmenopausal; a postmenopausal woman is defined as a woman who has
   experienced amenorrhea > 12 consecutive months or a woman on hormone replacement
   therapy with documented FSH level > 35 mIU/mL (women of childbearing potential must
   have a pregnancy test within 28 days prior to registration, and must use an adequate
   method of contraception to avoid pregnancy throughout the study and for a period of at
   least 3 months after the study)

   - Provide signed written informed consent

   - Willingness to undergo bone marrow examination on day 8 of first induction cycle

   - WBC < 10,000/uL (patients with WBC >= 10,000/uL must undergo cytoreduction with
   hydroxyurea prior to enrollment and will not be enrolled if the WBC remains >=
   10,000/uL (of note, patients with symptoms/signs of hyperleukocytosis or WBC >
   100,000/uL can be treated with leukapheresis prior to enrollment)

Exclusion Criteria:

   - Diagnosis of another malignancy, unless the patient was diagnosed at least 2 years
   earlier and has been disease-free for at least 6 months following the completion of
   curative intent therapy; there should be no plan to begin therapy for the prior
   malignancy at the time of study registration; prior treatment with AML induction-type
   chemotherapy is not allowed (note the following exceptions: patients with treated
   non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia,
   regardless of the disease-free duration, are eligible for this study if definitive
   treatment for the condition has been completed; patients with organ-confined prostate
   cancer with no evidence of recurrent or progressive disease based on prostate-specific
   antigen [PSA] values are also eligible for this study if hormonal therapy has been
   initiated or a radical prostatectomy has been performed; concurrent hormonal therapy
   is allowed)

   - Myeloid blast crisis of chronic myelogenous leukemia (CML)

   - Prior systemic chemotherapy for AML with the exception of hydroxyurea

   - Prior treatment with AML induction-type chemotherapy, GO, HDAC inhibitors, or high
   dose chemotherapy with hematopoietic stem cell support

   - Treatment with HDAC inhibitors during the last 3 years prior to registration,
   including the use of valproic acid for seizure activity or other purposes

   - Known hypersensitivity to hydroxyurea, GO, or vorinostat

   - Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia
   unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal
   fluid (CSF)

   - Prior positive test for the human immunodeficiency virus (HIV)

   - Breastfeeding

   - Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
   exhibiting ongoing signs/symptoms related to the infection and without improvement,
   despite appropriate antibiotics or other treatment)