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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.
 
ClinicalTrials.gov Identifier: NCT00005962
Recruitment Status : Completed
First Posted : November 5, 2003
Last Update Posted : August 20, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Eastern Cooperative Oncology Group

Tracking Information
First Submitted Date  ICMJE July 5, 2000
First Posted Date  ICMJE November 5, 2003
Last Update Posted Date August 20, 2013
Study Start Date  ICMJE July 2000
Actual Primary Completion Date October 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison of Three Treatment Regimens in Treating Patients With Relapsed or Refractory Acute Myelogenous Leukemia
Official Title  ICMJE A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia
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.

Detailed Description

OBJECTIVES:

  • 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Biological: sargramostim
  • Drug: cyclophosphamide
  • Drug: cytarabine
  • Drug: gemtuzumab ozogamicin
  • Drug: liposomal daunorubicin citrate
  • Drug: topotecan hydrochloride
Study Arms  ICMJE Not Provided
Publications *

*   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 Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2007
Actual Primary Completion Date October 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • 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)

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

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

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • 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

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior gemtuzumab ozogamicin

Chemotherapy:

  • 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

Radiotherapy:

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

Surgery:

  • Not specified
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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 Puerto Rico,   South Africa,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00005962
Other Study ID Numbers  ICMJE CDR0000067944
E-4999
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Eastern Cooperative Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Mark R. Litzow, MD Mayo Clinic
PRS Account Eastern Cooperative Oncology Group
Verification Date August 2013

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