Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Related Clinical Trial
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia AML Therapy With Irradiated Allogeneic Cells Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission Genetic and Molecular Characteristics of Mexican Adults With Acute Myeloid Leukemia: a Prospective Multicentric Study. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)

Brief Title

Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Official Title

Phase II Trial of Vorinostat (Suberoylanilide Hydroxamic Acid or SAHA; Zolinza™) in Combination With Gemtuzumab Ozogamicin (Mylotarg™) as Induction and Post-Remission Therapy in Older Patients With Previously Untreated Non-M3 Acute Myeloid Leukemia

Brief 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.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the CR/CRi rate after treatment with vorinostat plus GO. (Good risk group)
      II. To determine the 30-day survival after treatment with vorinostat plus GO. (Poor risk
      group)

      SECONDARY OBJECTIVES:

      I. To estimate the frequency and severity of regimen-associated toxicities, along with 30-day
      survival after start of treatment with vorinostat plus GO. (Good risk group) II. To determine
      the CR/CRi rate after treatment with vorinostat plus GO, and estimate the frequency and
      severity of regimen-associated toxicities. (Poor risk group) III. To investigate the
      relapse-free survival of patients who achieve CR/CRi and receive maintenance therapy on this
      study.

      IV. To define cellular factors associated with clinical response to GO/vorinostat and
      determine the mechanisms underlying the synergistic effect between GO and vorinostat on
      primary AML cells (in vitro correlative and mechanistic studies).

      OUTLINE:

      REMISSION INDUCTION THERAPY: Patients receive oral vorinostat once daily on days 1-9 and
      gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 15-22 days for up to
      3 courses.

      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.

      MAINTENANCE THERAPY: Patients receive oral vorinostat once daily on days 1-14. Treatment
      repeats every 28 days for 4 courses.

      All treatment continues in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for up to 3
      years.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of Participants Achieving CR or CRi With Induction Therapy (Good-risk Group)

Secondary Outcome

 Relapse-free Survival (Good- and Poor-risk Group)

Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

gemtuzumab ozogamicin

Study Arms / Comparison Groups

 Arm I
Description:  REMISSION INDUCTION THERAPY: Patients receive oral vorinostat once daily on days 1-9 and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 15-22 days for up to 3 courses. .
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.
MAINTENANCE THERAPY: Patients receive oral vorinostat once daily on days 1-14. Treatment repeats every 28 days for 4 courses.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

31

Start Date

March 2008


Primary Completion Date

August 2010

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)
      

Gender

All

Ages

60 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Roland Walter, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00673153

Organization ID

2200.00

Secondary IDs

NCI-2010-00401

Responsible Party

Principal Investigator

Study Sponsor

Fred Hutchinson Cancer Research Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Roland Walter, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


Verification Date

May 2017