Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

Inclusion Criteria:

* Prior morphological diagnosis of acute myeloid leukemia (AML) other then acute promyelocytic leukemia (APL) according to the 2001 WHO criteria; patients with biphenotypic AML are eligible
* Need for first salvage chemotherapy for persistent or relapsing disease, defined by standard criteria, after at least one course of conventional chemotherapy
* A bone marrow biopsy is not required but should be obtained if the aspirate is dilute, hypocellular, or not aspirable; outside marrow exams performed within the stipulated time period are acceptable if the slides are reviewed at the study institution
* Flow cytometric analysis of the marrow aspirate per institutional practice guidelines
* Duration of first complete remission (CR1) \< 12 months (or primary resistant disease)
* Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) if relapse occurs 6-12 months post-transplant
* ECOG/WHO/Zubrod performance status of 0-3 within 14 days prior to registration
* Off any active therapy for AML except hydroxyurea for at least 14 days prior to study registration, with resolution of all grade 3 and 4 non-hematological toxicities
* Willingness to discontinue taking any medications known to cause a risk of Torsades de Pointes
* Bilirubin =\< 1.5 x Institutional Upper Limit of Normal (IULN) unless elevation is due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (within 7 days prior to registration)
* SGOT (AST) and SGPT (ALT) =\< 1.5 x IULN unless elevation is due to hepatic infiltration by AML (within 7 days prior to registration)
* Serum creatinine =\< 1.5 x IULN (within 7 days prior to registration)
* No clinical or radiographical evidence of heart failure
* white blood cell (WBC) \< 25,000/uL within 3 days prior to registration
* 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; peripheral blood only is acceptable if the peripheral blast count is \> 5,000/uL and \> 50% of total WBC
* Must agree to use adequate contraception prior to and during the study
* Can understand and sign a written informed consent document; a legally authorized representative can provide consent if the patient is unable

Exclusion Criteria:

* Remission or second or later relapse
* Diagnosis of another malignancy, unless diagnosed at least 2 years earlier and disease-free for at least 6 months after completion of curative intent therapy except:

  * Treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, if definitive treatment has been completed
  * Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or a radical prostatectomy was performed
* Refractory/relapsing blast crisis of chronic myeloid 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
* Possible central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms no leukemic blasts in the cerebralspinal fluid (CSF)
* HIV-positive patients with cluster of differentiation (CD)4 count is \< 200 cells/uL or if AIDS-related complications
* Pregnancy; breastfeeding should be discontinued if the mother is treated with vorinostat, azacitidine, and GO
* Uncontrolled systemic infection, despite appropriate antibiotics or other treatment)
* Receipt of any other investigational agents