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