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