Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Condition: Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute
Intervention: gemtuzumab ozogamicin; vorinostat; laboratory biomarker analysis
Intervention description: Given IV; Given orally; Correlative studies
Intervention MeSH terms: Vorinostat; Gemtuzumab; Calicheamicins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      RATIONALE: Vorinostat may stop the growth of cancer cells by interfering with various
      proteins needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin (GO),
      can block cancer growth in different ways. GO finds cancer cells and helps kill them by
      carrying a cancer-killing substance to them. Giving vorinostat together with gemtuzumab
      ozogamicin may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving vorinostat together with gemtuzumab
      ozogamicin works in treating older patients with previously untreated acute myeloid leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Morphological diagnosis of AML other then acute promyelocytic leukemia (FAB M3)
             according to WHO diagnostic criteria; diagnosis of AML must be based on bone marrow or
             peripheral blood studies obtained within 28 days prior to study registration or start
             of hydroxyurea (for patients presenting with WBC >= 10,000/uL), and no potentially
             anti-leukemic therapy (with the exception of hydroxyurea) must have been given between
             AML diagnosis and study registration; a bone marrow biopsy is not routinely required
             but should be obtained if the aspirate is dilute, hypocellular, or inaspirable;
             outside bone marrows performed within the stipulated time period are acceptable as
             long as the slides are reviewed at a study institution

          -  Cytogenetic analysis on bone marrow or peripheral blood specimen is available; based
             on the result from the first interim analysis, patients stratified into the good-risk
             group are only eligible if their AML has favorable cytogenetics (core-binding factor
             AML) or has a normal karyotype; patients stratified into the poor-risk group are
             eligible independent of the cytogenetic analysis

          -  Pretreatment bone marrow and peripheral blood specimens for correlative studies are
             available; if bone marrow was performed at an outside facility, submission of
             peripheral blood only is acceptable as long as the peripheral blast count is >
             5,000/uL and > 50% of total WBC

          -  Patients with a history of antecedent MDS are eligible, if prior treatment did not
             include intensive chemotherapy; patients may have received hematopoietic growth
             factors, thalidomide/lenalidomide, 5-azacytidine/decitabine, arsenic trioxide, signal
             transduction inhibitors, or low dose cytarabine (< 100 mg/m2/day) for treatment of
             MDS; patients must be off prior therapy for MDS at least 30 days prior to study
             registration, and all non-hematologic toxicities must have resolved to < grade 2

          -  ECOG/WHO/Zubrod performance status of 0-3

          -  Bilirubin =< 2.5 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 14 days prior to registration)

          -  SGOT (AST) and SPGT (ALT) =< 1.5 x IULN unless elevation is thought to be due to
             hepatic infiltration by AML (assessed within 14 days prior to registration)

          -  Serum creatinine =< 1.5 x IULN (assessed within 14 days prior to registration)

          -  Left ventricular ejection fraction >= 40% and no clinical evidence of congestive heart
             failure (assessed within 28 days prior to registration, e.g. by MUGA scan or
             echocardiography)

          -  Men of reproductive potential must use an effective contraceptive method throughout
             the study and for a period of at least 3 months after the study

          -  Women must be postmenopausal; a postmenopausal woman is defined as a woman who has
             experienced amenorrhea > 12 consecutive months or a woman on hormone replacement
             therapy with documented FSH level > 35 mIU/mL (women of childbearing potential must
             have a pregnancy test within 28 days prior to registration, and must use an adequate
             method of contraception to avoid pregnancy throughout the study and for a period of at
             least 3 months after the study)

          -  Provide signed written informed consent

          -  Willingness to undergo bone marrow examination on day 8 of first induction cycle

          -  WBC < 10,000/uL (patients with WBC >= 10,000/uL must undergo cytoreduction with
             hydroxyurea prior to enrollment and will not be enrolled if the WBC remains >=
             10,000/uL (of note, patients with symptoms/signs of hyperleukocytosis or WBC >
             100,000/uL can be treated with leukapheresis prior to enrollment)

        Exclusion Criteria:

          -  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; there should be no plan to begin therapy for the prior
             malignancy at the time of study registration; prior treatment with AML induction-type
             chemotherapy is not allowed (note 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; concurrent hormonal therapy
             is allowed)

          -  Myeloid blast crisis of chronic myelogenous leukemia (CML)

          -  Prior systemic chemotherapy for AML with the exception of hydroxyurea

          -  Prior treatment with AML induction-type chemotherapy, GO, HDAC inhibitors, or high
             dose chemotherapy with hematopoietic stem cell support

          -  Treatment with HDAC inhibitors during the last 3 years prior to registration,
             including the use of valproic acid for seizure activity or other purposes

          -  Known hypersensitivity to hydroxyurea, GO, or vorinostat

          -  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)

          -  Prior positive test for the human immunodeficiency virus (HIV)

          -  Breastfeeding

          -  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)