• Complete remission (CR) or CR with incomplete blood count recovery (CRi) rate (Good risk group) [ Designated as safety issue: No ]
  
• 30-day survival (Poor risk group) [ Designated as safety issue: No ]
  

• 30-day survival (Good risk group) [ Designated as safety issue: No ]
  
• CR/CRi rate (Poor risk group) [ Designated as safety issue: No ]
  
• Frequency and severity of regimen-associated toxicities [ Designated as safety issue: Yes ]
  
• Relapse-free survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the complete remission (CR)/CR with incomplete blood count recovery (CRi) rate in older patients with previously untreated acute myeloid leukemia (AML) treated with vorinostat and gemtuzumab ozogamicin. (Good risk group)
• Determine the 30-day survival of patients treated with this regimen. (Poor risk group)

Secondary

• Estimate the 30-day survival of patients treated with this regimen. (Good risk group)
• Determine the CR/CRi rate in patients treated with this regimen. (Poor risk group)
• Estimate the frequency and severity of regimen-associated toxicities in these patients.
• Investigate the relapse-free survival of patients who achieve CR/CRi and receive maintenance therapy on this study.
• Define cellular factors associated with clinical response to this treatment regimen and determine the mechanisms underlying the synergistic effect between gemtuzumab ozogamicin and vorinostat on primary AML cells (in vitro correlative and mechanistic studies).

OUTLINE: This is a multicenter study. Patients are stratified according to risk status (good risk [60-69 years of age OR ECOG/WHO/ZUBROD performance status (PS) 0-1] vs poor risk [%u2265 70 years of age AND ECOG/WHO/ZUBROD PS 2-3]).

• Remission induction therapy: Patients receive oral vorinostat once daily on days 1-9 and gemtuzumab ozogamicin IV over 2 hours on day 8 in the absence of disease progression or unacceptable toxicity. Patients achieving a complete remission (CR) or CR with incomplete blood count recovery (CRi) proceed to consolidation therapy. Patients with residual leukemia (%u2265 5% blasts) and no hypocellularity receive a second course of induction therapy beginning between days 15-22. Patients achieving a CR or CRi after the second course proceed to consolidation therapy. Patients with continued persistent disease (%u2265 5% blasts) are removed from the study.
• Consolidation therapy: Beginning within 60 days after the completion of remission induction therapy, patients receive oral vorinostat once daily on days 1-9 and gemtuzumab ozogamicin IV over 2 hours on day 8 in the absence of disease progression or unacceptable toxicity. Patients who remain in CR or CRi proceed to maintenance therapy.
• Maintenance therapy: Patients receive oral vorinostat once daily on days 1-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 1 year.

DISEASE CHARACTERISTICS:

• Morphological diagnosis of acute myeloid leukemia (AML)

  • No acute promyelocytic leukemia (FAB M3)
• Previously untreated disease
• Patients with a history of antecedent myelodysplastic syndrome are eligible, if prior treatment did not include intensive chemotherapy AND patients are off therapy for %u2265 30 days prior to study registration
• No myeloid blast crisis of chronic myelogenous leukemia
• No clinical evidence suggestive of CNS involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid

PATIENT CHARACTERISTICS:

• ECOG/WHO/Zubrod performance status 0-3

• WBC < 10,000/%u03BCL

  • Patients with WBC %u226510,000/%u03BCL must undergo cytoreduction with hydroxyurea prior to study enrollment
  • Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/%u03BCL may be treated with leukapheresis prior to study enrollment
• Bilirubin %u2264 2.5 times upper limit of normal (ULN) (unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis)
• ALT and AST %u2264 1.5 times ULN (unless elevation is thought to be due to hepatic infiltration by AML)
• Serum creatinine %u2264 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for %u2265 3 months after completion of study therapy
• LVEF %u2265 40%
• No clinical evidence of congestive heart failure

• No other malignancy unless the patient was diagnosed %u2265 2 years ago AND has been disease-free for %u2265 6 months following the completion of curative intent therapy

  • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia are eligible provided definitive treatment for the condition has been completed
  • Patients with organ-confined prostate cancer are eligible provided there is no evidence of recurrent or progressive disease, based on prostate-specific antigen (PSA) values, AND hormonal therapy has been initiated or a radical prostatectomy has been performed
• No known hypersensitivity to hydroxyurea, gemtuzumab ozogamicin, or vorinostat
• No HIV positivity
• No uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection AND infection has not improved despite appropriate antibiotics or other treatment)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy for AML, except for hydroxyurea
• No prior treatment with AML induction-type chemotherapy, gemtuzumab ozogamicin, or high-dose chemotherapy with hematopoietic stem cell support
• More than 3 years since prior treatment with histone deacetylase inhibitors (HDACi), including the use of valproic acid for seizure activity or other purposes