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Clinical Trials (PDQ®)

Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia

Basic Trial Information
Trial Description
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentCompleted50 and overNCINCI-2012-01147
IR-6921, CDR0000642213, 2288.00, 8297, P30CA015704, FHCRC-2288.00, NCT00895934

Trial Description


The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people.

Further Study Information


I. Determine the vorinostat dose with the most favorable efficacy and toxicity when combined with azacitidine and GO.


I. Describe the complete response (CR)/ CR with inadequate recovery (Cri) rate after a total of 6 cycles of therapy.

II. Describe the disease-free survival of patients that achieve CR/CRi. III. Determine whether acute myeloid leukemia (AML) characteristics associated with preclinical GO efficacy predict for clinical benefit, and assess whether differentiation-inducing agents modulate these characteristics and lower the apoptotic threshold for calicheamicin-gamma1-induced cytotoxicity (in vitro correlative and mechanistic studies).

OUTLINE: This is phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) on days 1-9, azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

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

Eligibility Criteria

Inclusion Criteria:

  • Prior morphological diagnosis of AML other then acute promyelocytic leukemia according to the 2001 World Health Organization (WHO) diagnostic criteria; patients with biphenotypic AML are eligible
  • Requiring first salvage chemotherapy for persistent or relapsing disease, as defined by standard criteria, after at least one course of conventional chemotherapy, e.g. with "7+3"
  • A bone marrow biopsy is not routinely required, but should be obtained if the aspirate is dilute, hypocellular, or inaspirable; outside bone marrow examinations performed within the stipulated time period are acceptable as long as the slides are reviewed at the study institution
  • Flow cytometric analysis of the bone marrow aspirate should be performed according to institutional practice guidelines
  • Duration of CR1 < 12 months (or primary resistant disease)
  • Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs 6-12 months post-transplant
  • Eastern Cooperative Oncology Group (ECOG)/WHO/Zubrod performance status of 0-3, assessed within 14 days prior to registration
  • Must be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration, and all grade 3 and 4 non-hematological toxicities must have resolved
  • Willingness to discontinue taking any medications that are generally accepted to have a risk causing Torsades de Pointes during the study
  • Bilirubin =< 1.5 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 7 days prior to registration
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 1.5 x IULN unless elevation is thought to be due to hepatic infiltration by AML (assessed within 7 days prior to registration)
  • Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to registration)
  • No clinical or radiographical evidence of heart failure
  • White blood cell count (WBC) < 25,000/uL, assessed within 3 days prior to registration; patients with WBC >= 25,000/uL must undergo cytoreduction with hydroxyurea prior to enrollment and will not be treated if the WBC remains >= 25,000/ uL despite hydroxyurea treatment
  • 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; submission of peripheral blood only is acceptable as long as the peripheral blast count is > 5,000/uL and blast count > 50% of total WBC
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document; the consent can be obtained from a legally authorized representative if the patient is unable to provide informed consent

Exclusion Criteria:

  • Patients in remission or with second or later relapse
  • 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 with 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
  • Refractory/relapsing blast crisis of chronic myelogenous 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
  • 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)
  • Human immunodeficiency virus (HIV)-positive patients are excluded if their cluster of differentiation (CD)4 count is below 200 cells/uL or if they have active acquired immune deficiency syndrome (AIDS)-related complications, as these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
  • Pregnancy; women of child-bearing potential must undergo pregnancy test within 7 days prior to registration; breastfeeding should be discontinued if the mother is treated with vorinostat, azacitidine, and GO
  • 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)
  • Patients may not be receiving any other investigational agents

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Roland WalterPrincipal Investigator

Link to the current record.
NLM Identifer NCT00895934 processed this data on November 12, 2014

Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to

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