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Comparison of Three Treatment Regimens in Treating Patients With Relapsed or Refractory Acute Myelogenous 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. Identifier: NCT00005962
Recruitment Status : Completed
First Posted : November 5, 2003
Last Update Posted : August 20, 2013
National Cancer Institute (NCI)
Information provided by:
Eastern Cooperative Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining more than one drug or combining monoclonal antibody with chemotherapy may kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia.

PURPOSE: Randomized phase II trial to compare the effectiveness of three treatment regimens in treating patients who have relapsed or refractory acute myelogenous leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Biological: sargramostim Drug: cyclophosphamide Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: liposomal daunorubicin citrate Drug: topotecan hydrochloride Phase 2

Detailed Description:


  • Compare the rates of complete response (CR) and CR without full platelet recovery in patients with relapsed or refractory acute myelogenous leukemia treated with gemtuzumab ozogamicin and cytarabine vs daunorubicin liposomal and cytarabine vs cyclophosphamide, cytarabine, and topotecan.
  • Compare the toxicities of these 3 regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by disease status (relapse less than 6 months after first complete response (CR) vs relapse 6-12 months after first CR vs refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course) vs second or greater relapse).

  • Induction: Patients are randomized to 1 of 3 treatment arms:

    • Arm I: Patients receive cytarabine IV over 2 hours on days 1-4 and gemtuzumab ozogamicin IV over 2 hours on day 5.
    • Arm II: Patients receive daunorubicin liposomal IV over a minimum of 2 hours on days 1-3 and cytarabine IV over 2 hours (beginning immediately after completion of daunorubicin liposomal infusion) on days 1-4.
    • Arm III: Patients receive cyclophosphamide IV over 1 hour every 12 hours on days 1-3, cytarabine IV over 2 hours (beginning immediately after completion of cyclophosphamide infusion) on days 2-6, and topotecan IV continuously on days 2-6.
  • Consolidation: Patients who achieve complete remission (CR) receive 1 additional course of induction therapy on the same arm to which they were originally randomized beginning within 4-6 weeks after initial documentation of CR. Patients on arm II receive no additional daunorubicin liposomal if resting ejection fraction is less than 50% preconsolidation. All patients receive sargramostim (GM-CSF) IV over 4 hours or SQ daily beginning 24 hours after completion of consolidation therapy and continuing until blood counts recover.

Patients are followed every 3 months through year 2, every 6 months through year 5, and then annually thereafter until death.

PROJECTED ACCRUAL: A maximum of 150-165 patients (50-55 per arm) will be accrued for this study within 2 years.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia
Study Start Date : July 2000
Actual Primary Completion Date : October 2005
Actual Study Completion Date : June 2007

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven acute myelogenous leukemia of one of the following types:

    • Acute myeloblastic leukemia (FAB type M0, M1, or M2)
    • Acute promyelocytic leukemia (FAB type M3) allowed if ineligible for an ECOG M3 protocol or if no tretinoin or arsenic trioxide therapy is planned
    • Acute myelomonocytic leukemia (FAB type M4)
    • Acute monocytic leukemia (FAB type M5)
    • Acute erythroleukemia (FAB type M6)
    • Acute megakaryocytic leukemia (FAB type M7)
  • Must meet 1 of the following criteria:

    • Relapse less than 6 months after first complete remission (CR)
    • Relapse 6-12 months after first CR
    • Refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course)

      • Must have marrow documentation of residual leukemia after chemotherapy (for at least 2 weeks duration)
    • Second or greater relapse
  • No relapse greater than 1 year after achieving first CR
  • Blast cells must be CD33 positive
  • Prior CNS leukemia allowed if there is currently documentation of no CNS involvement on CSF examination (i.e., negative CSF by lumbar puncture)



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • See Disease Characteristics


  • Bilirubin no greater than 2.0 mg/dL*
  • SGOT less than 2 times upper limit of normal* NOTE: *Unless due to leukemia infiltration


  • Creatinine no greater than 2.0 mg/dL


  • See Chemotherapy
  • No myocardial infarction within the past 3 months
  • No significant congestive heart failure
  • No significant cardiac arrhythmia
  • Cardiac ejection fraction normal by MUGA scan or echocardiogram
  • Resting ejection fraction at least 50% or at least 5% increase with exercise
  • Shortening fraction at least 24% or normal by echocardiogram


  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No concurrent organ damage or other medical problems that would precludestudy therapy
  • No concurrent evidence (including positive blood or deep tissue cultures or stains) of invasive fungal infection
  • No hypersensitivity to ingredients of gemtuzumab ozogamicin or daunorubicin liposomal
  • No other active tumor that would interfere with study therapy or increase risk


Biologic therapy:

  • No prior gemtuzumab ozogamicin


  • See Disease Characteristics
  • See Biologic therapy
  • No prior daunorubicin liposomal or topotecan
  • Prior doxorubicin (no greater than 300 mg/m2), daunorubicin (no greater than 300 mg/m2), idarubicin (no greater than 100 mg/m2), or mitoxantrone (no greater than 100 mg/m2) allowed if left ventricular function is adequate
  • At least 4 weeks since prior chemotherapy except patients who are refractory to conventional initial induction chemotherapy
  • Prior hydroxyurea allowed within 4 weeks prior to beginning study
  • Hydroxyurea must be discontinued at least 24 hours prior to beginning study

Endocrine therapy:

  • Not specified


  • At least 4 weeks since prior radiotherapy except patients who are refractory to conventional initial induction chemotherapy


  • Not specified

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005962

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Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
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Study Chair: Mark R. Litzow, MD Mayo Clinic

Publications of Results:
Litzow MR, Goloubeva O, Rowe J, et al.: A randomized phase II trial of gemtuzumab ozogamicin vs. liposomal daunorubicin vs. cyclophosphamide plus topotecan, each combined with intermediate dose Ara-C for the treatment of patients with relapsed or refractory acute myelogenous leukemia . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2359, 2003.

Layout table for additonal information Identifier: NCT00005962    
Other Study ID Numbers: CDR0000067944
First Posted: November 5, 2003    Key Record Dates
Last Update Posted: August 20, 2013
Last Verified: August 2013
Keywords provided by Eastern Cooperative Oncology Group:
recurrent adult acute myeloid leukemia
adult acute erythroid leukemia (M6)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute promyelocytic leukemia (M3)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute megakaryoblastic leukemia (M7)
adult acute monocytic leukemia (M5b)
adult acute minimally differentiated myeloid leukemia (M0)
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Antineoplastic Agents, Immunological