A Phase 1/2 Study of Vorinostat (Zolinza®) in Combination With Gemtuzumab Ozogamicin (Mylotarg®) and Azacitidine (Vidaza®) in Patients 50 Years of Age and Older With Relapsed/Refractory Non-APL Acute Myeloid Leukemia (AML)

Inclusion Criteria:

- Prior morphological diagnosis of AML other then acute promyelocytic leukemia
according to the 2001 World Health Organization (WHO) diagnostic criteria; patients
with biphenotypic AML are eligible

- Requiring first salvage chemotherapy for persistent or relapsing disease, as defined
by standard criteria, after at least one course of conventional chemotherapy, e.g.
with "7+3"

- A bone marrow biopsy is not routinely required, but should be obtained if the
aspirate is dilute, hypocellular, or inaspirable; outside bone marrow examinations
performed within the stipulated time period are acceptable as long as the slides are
reviewed at the study institution

- Flow cytometric analysis of the bone marrow aspirate should be performed according to
institutional practice guidelines

- Duration of CR1 < 12 months (or primary resistant disease)

- Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT)
are eligible if relapse occurs 6-12 months post-transplant

- Eastern Cooperative Oncology Group (ECOG)/WHO/Zubrod performance status of 0-3,
assessed within 14 days prior to registration

- Must be off any active therapy for AML with the exception of hydroxyurea for at least
14 days prior to study registration, and all grade 3 and 4 non-hematological
toxicities must have resolved

- Willingness to discontinue taking any medications that are generally accepted to have
a risk causing Torsades de Pointes during the study

- Bilirubin =< 1.5 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 7 days prior to registration

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 1.5 x
IULN unless elevation is thought to be due to hepatic infiltration by AML (assessed
within 7 days prior to registration)

- Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to registration)

- No clinical or radiographical evidence of heart failure

- White blood cell count (WBC) < 25,000/uL, assessed within 3 days prior to
registration; patients with WBC >= 25,000/uL must undergo cytoreduction with
hydroxyurea prior to enrollment and will not be treated if the WBC remains >= 25,000/
uL despite hydroxyurea treatment

- Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/uL can be treated
with leukapheresis prior to enrollment

- Collection of bone marrow and peripheral blood specimens for correlative studies
prior to study treatment is highly recommended; submission of peripheral blood only
is acceptable as long as the peripheral blast count is > 5,000/uL and blast count >
50% of total WBC

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

- Ability to understand and the willingness to sign a written informed consent
document; the consent can be obtained from a legally authorized representative if the
patient is unable to provide informed consent

Exclusion Criteria:

- Patients in remission or with second or later relapse

- 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 with 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

- Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML)

- Prior anti-AML treatment with GO, histone deacetylase (HDAC) inhibitor (including the
use of valproic acid for control of seizure activity or other purposes), or
demethylating agent

- Known hypersensitivity to GO, vorinostat, azacitidine, or mannitol

- 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)

- Human immunodeficiency virus (HIV)-positive patients are excluded if their cluster of
differentiation (CD)4 count is below 200 cells/uL or if they have active acquired
immune deficiency syndrome (AIDS)-related complications, as these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy

- Pregnancy; women of child-bearing potential must undergo pregnancy test within 7 days
prior to registration; breastfeeding should be discontinued if the mother is treated
with vorinostat, azacitidine, and GO

- 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)

- Patients may not be receiving any other investigational agents