Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00673153
Recruitment Status : Terminated
First Posted : May 7, 2008
Results First Posted : June 1, 2017
Last Update Posted : June 1, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roland Walter, Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE May 6, 2008
First Posted Date  ICMJE May 7, 2008
Results First Submitted Date  ICMJE March 15, 2017
Results First Posted Date  ICMJE June 1, 2017
Last Update Posted Date June 1, 2017
Study Start Date  ICMJE March 2008
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
  • Number of Participants Achieving CR or CRi With Induction Therapy (Good-risk Group) [ Time Frame: after completion of induction therapy, administered every 21-42 days for up to two courses ]
  • Number of Participants Alive at Day 30 (Poor-risk Group) [ Time Frame: At day 30 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2008)
  • Complete remission (CR) or CR with incomplete blood count recovery (CRi) rate (Good risk group)
  • 30-day survival (Poor risk group)
Change History Complete list of historical versions of study NCT00673153 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
  • Relapse-free Survival (Good- and Poor-risk Group) [ Time Frame: At relapse ]
  • Number of Participants Achieving CR or CRi With Induction Therapy (Poor-risk Group) [ Time Frame: after completion of induction therapy, administered every 21-42 days for up to two courses ]
  • Number of Participants Alive at Day 30 (Good-risk Group) [ Time Frame: At day 30 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2008)
  • 30-day survival (Good risk group)
  • CR/CRi rate (Poor risk group)
  • Frequency and severity of regimen-associated toxicities
  • Relapse-free survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: gemtuzumab ozogamicin
    Given IV
    Other Names:
    • Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
    • CDP-771
    • CMA-676
    • hP67.6-Calicheamicin
    • Mylotarg
    • WAY-CMA-676
  • Drug: vorinostat
    Given orally
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE Experimental: Arm I

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.

Interventions:
  • Drug: gemtuzumab ozogamicin
  • Drug: vorinostat
  • Other: laboratory biomarker analysis
Publications * Walter RB, Medeiros BC, Powell BL, Schiffer CA, Appelbaum FR, Estey EH. Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia. Haematologica. 2012 May;97(5):739-42. doi: 10.3324/haematol.2011.055822. Epub 2011 Dec 1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 30, 2017)
31
Original Enrollment  ICMJE
 (submitted: May 6, 2008)
107
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00673153
Other Study ID Numbers  ICMJE 2200.00
NCI-2010-00401 ( Registry Identifier: National Cancer Institute (NCI) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Roland Walter, Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Roland Walter Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP