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S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML

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ClinicalTrials.gov Identifier: NCT00085709
Recruitment Status : Completed
First Posted : June 16, 2004
Results First Posted : August 27, 2012
Last Update Posted : September 30, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Tracking Information
First Submitted Date  ICMJE June 14, 2004
First Posted Date  ICMJE June 16, 2004
Results First Submitted Date  ICMJE June 5, 2012
Results First Posted Date  ICMJE August 27, 2012
Last Update Posted Date September 30, 2015
Study Start Date  ICMJE July 2004
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2012)
  • 2-year Disease-free Survival (DFS) [ Time Frame: After completing any treatment, every 6 months for 2 years, than annually for years 3-5 ]
    Measured from data of randomization to post-consolidation therapy until relapse from complete response or death from any cause, with observations censored at the date of last contact for patients last known to be alive without report of relapse.
  • Complete Remission [ Time Frame: After induction therapy was completed (1 or 2 months) ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00085709 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2012)
Toxicity [ Time Frame: For induction, daily for the first 10 days, then twice weekly until consolidation treatment. Weekly during consolidation treatment. Weekly if randomized to post-consolidation G.O. ]
Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
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 S0106 Cytarabine and Daunorubicin w/ or w/o Gemtuzumab Followed By HD Cytarabine and Either Gemtuzumab or Nothing in de Novo AML
Official Title  ICMJE A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg®) During Induction Therapy Versus Standard Induction With Daunomycin and Cytosine Arabinoside Followed by Consolidation and Subsequent Randomization to Post-Consolidation Therapy With Gemtuzumab Ozogamicin (Mylotarg®) or No Additional Therapy For Patients Under Age 61 With Previously Untreated De Novo Acute Myeloid Leukemia (AML)
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop cancer cells from dividing so they stop growing and 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 chemotherapy with gemtuzumab ozogamicin may kill more cancer cells. It is not yet known whether induction therapy using cytarabine and daunorubicin is more effective with or without gemtuzumab ozogamicin or whether postconsolidation therapy using gemtuzumab ozogamicin is more effective than no additional therapy in treating de novo (first occurrence) acute myeloid leukemia.

PURPOSE: This randomized phase III trial is comparing two different regimens of chemotherapy and monoclonal antibody therapy to see how well they work in treating patients with previously untreated de novo acute myeloid leukemia.

Detailed Description

OBJECTIVES:

  • Compare disease-free survival of patients with previously untreated de novo acute myeloid leukemia treated with induction therapy comprising cytarabine and daunorubicin with vs without gemtuzumab ozogamicin followed by consolidation therapy comprising high-dose cytarabine and post-consolidation therapy comprising gemtuzumab ozogamicin vs no additional therapy.
  • Compare the complete remission rate in patients treated with these regimens.
  • Compare the frequency and severity of the toxic effects of these regimens in these patients.

Other objectives (if funding allows):

  • Determine the prognostic significance of CD33 expression on the response rate in patients receiving gemtuzumab ozogamicin.
  • Determine the prognostic significance of FLT3 mutations in these patients before treatment with these regimens.
  • Determine the prognostic significance of minimal residual disease in remission specimens from these patients treated with these regimens.
  • Determine the prognostic significance of the flow cytometric detection of minimal residual disease in specimens collected from these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified during induction therapy according to age (< 35 years vs ≥ 35 years) and during post-consolidation therapy according to preinduction cytogenetic risk group.

  • Induction therapy: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive daunorubicin IV on days 1-3, cytarabine IV continuously on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4. Patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously once daily beginning on day 15 and continuing until blood counts recover.
    • Arm II: Patients receive daunorubicin, cytarabine, and G-CSF or GM-CSF as in arm I.

Patients in both arms undergo bone marrow aspiration and biopsy on day 14 (and on day 19, if applicable) and then proceed to reinduction therapy.

  • Reinduction therapy: Patients receive daunorubicin IV on days 1-3 and cytarabine IV continuously on days 1-7. Patients also receive G-CSF or GM-CSF as in induction therapy.

Patients who achieve A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy.

  • Consolidation therapy: Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients who maintain A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status after consolidation therapy proceed to post-consolidation therapy.

  • Post-consolidation therapy: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
    • Arm II: Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 684 patients (342 per treatment arm) will be accrued for this study within 4.5-5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: gemtuzumab ozogamicin
    Given IV, induction Arm1 6mg/m2 D4; post-consolidation 5mg/m2 3 doses >/= 28 days apart
    Other Name: mylotarg
  • Other: observation
    No treatment given
  • Drug: Cytosine arabinoside
    IV; induction Arms1/2 and reinduction 100 mg/m2/d days 1-7; consolidation 3gm/m2 q3hrs D1, 3, 5
    Other Name: Ara-C
  • Drug: Daunomycin
    IV; induction Arm1 45mg/m2 D1-3; Arm2 and reinduction 60 mg/m2 D1-3;
    Other Name: daunorubicin
Study Arms  ICMJE
  • Experimental: Post-consolidation GO
    Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
    Intervention: Drug: gemtuzumab ozogamicin
  • Post-consolidation observation
    Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization.
    Intervention: Other: observation
  • Active Comparator: Induction 7+3
    Standard induction regimen of 7 days of Ara-C (cytosine arabinoside) and 3 days of daunomycin
    Interventions:
    • Drug: Cytosine arabinoside
    • Drug: Daunomycin
  • Active Comparator: Induction 7+3+GO
    Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C and 3 days of daunomycin
    Interventions:
    • Drug: Cytosine arabinoside
    • Drug: Daunomycin
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
Actual Enrollment  ICMJE
 (submitted: October 30, 2012)
637
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date March 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Morphologically confirmed acute myeloid leukemia (AML) by bone marrow aspiration and biopsy* within the past 14 days

    • No M3 disease NOTE: *Patients with marked leukocytosis may be registered before the availability of biopsy results if the absolute blast count is ≥ 100,000 cells/µL
  • No blastic transformation of chronic myelogenous leukemia
  • No pre-existing hematologic disorder evolving to AML (e.g., myelodysplasia or secondary leukemia)

PATIENT CHARACTERISTICS:

Age

  • 18 to 60

Performance status

  • Zubrod 0-3

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • No known hepatitis B or C infection
  • No known liver disease

Renal

  • Not specified

Cardiovascular

  • LVEF ≥ 50% by MUGA or echocardiogram
  • No unstable cardiac arrhythmias
  • No unstable angina

Other

  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior systemic chemotherapy

    • Prior hydroxyurea to control high cell counts allowed
  • No more than 1 prior dose of intrathecal chemotherapy for acute leukemia
  • Concurrent intrathecal chemotherapy allowed during induction therapy

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00085709
Other Study ID Numbers  ICMJE S0106
U10CA032102 ( U.S. NIH Grant/Contract )
S0106 ( Other Identifier: SWOG )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Southwest Oncology Group
Study Sponsor  ICMJE Southwest Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Stephen H. Petersdorf, MD Seattle Cancer Care Alliance
PRS Account Southwest Oncology Group
Verification Date September 2015

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