Phase II Trial of Vorinostat (Suberoylanilide Hydroxamic Acid or SAHA; Zolinza™) in Combination With Gemtuzumab Ozogamicin (Mylotarg™) as Induction and Post-Remission Therapy in Older Patients With Previously Untreated Non-M3 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)