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NCT00085709 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2015-09-30

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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

2-year Disease-free Survival (DFS)

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outcome · POSTED

Complete Remission

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outcome · POSTED

Toxicity

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
maximum Age
60 Years
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
Treatment arms and interventions
arm Groups
  1. description
    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 Names
    1. Drug: gemtuzumab ozogamicin
    label
    Post-consolidation GO
    type
    EXPERIMENTAL
  2. description
    Patients receive no additional therapy. Patients are observed at days 30 and 60 after randomization.
    intervention Names
    1. Other: observation
    label
    Post-consolidation observation
    type
    OTHER
  3. description
    Standard induction regimen of 7 days of Ara-C (cytosine arabinoside) and 3 days of daunomycin
    intervention Names
    1. Drug: Cytosine arabinoside
    2. Drug: Daunomycin
    label
    Induction 7+3
    type
    ACTIVE_COMPARATOR
  4. description
    Gemtuzumab (GO) added to the standard induction regimen of 7 days of Ara-C and 3 days of daunomycin
    intervention Names
    1. Drug: Cytosine arabinoside
    2. Drug: Daunomycin
    label
    Induction 7+3+GO
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Post-consolidation GO
    description
    Given IV, induction Arm1 6mg/m2 D4; post-consolidation 5mg/m2 3 doses \>/= 28 days apart
    name
    gemtuzumab ozogamicin
    other Names
    1. mylotarg
    type
    DRUG
  2. arm Group Labels
    1. Post-consolidation observation
    description
    No treatment given
    name
    observation
    type
    OTHER
  3. arm Group Labels
    1. Induction 7+3
    2. Induction 7+3+GO
    description
    IV; induction Arms1/2 and reinduction 100 mg/m2/d days 1-7; consolidation 3gm/m2 q3hrs D1, 3, 5
    name
    Cytosine arabinoside
    other Names
    1. Ara-C
    type
    DRUG
  4. arm Group Labels
    1. Induction 7+3
    2. Induction 7+3+GO
    description
    IV; induction Arm1 45mg/m2 D1-3; Arm2 and reinduction 60 mg/m2 D1-3;
    name
    Daunomycin
    other Names
    1. daunorubicin
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
637
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    2-year Disease-free Survival (DFS)
    time Frame
    After completing any treatment, every 6 months for 2 years, than annually for years 3-5
  2. measure
    Complete Remission
    time Frame
    After induction therapy was completed (1 or 2 months)
secondary Outcomes
  1. description
    Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
    measure
    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.
Full study description
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.
Source references
references
  1. citation
    Dillon LW, Higgins J, Nasif H, Othus M, Beppu L, Smith TH, Schmidt E, Valentine Iii CC, Salk JJ, Wood BL, Erba HP, Radich JP, Hourigan CS. Quantification of measurable residual disease using duplex sequencing in adults with acute myeloid leukemia. Haematologica. 2024 Feb 1;109(2):401-410. doi: 10.3324/haematol.2023.283520.
    pmid
    37534515
    type
    DERIVED
  2. citation
    Zarnegar-Lumley S, Alonzo TA, Gerbing RB, Othus M, Sun Z, Ries RE, Wang J, Leonti A, Kutny MA, Ostronoff F, Radich JP, Appelbaum FR, Pogosova-Agadjanyan EL, O'Dwyer K, Tallman MS, Litzow M, Atallah E, Cooper TM, Aplenc RA, Abdel-Wahab O, Gamis AS, Luger S, Erba H, Levine R, Kolb EA, Stirewalt DL, Meshinchi S, Tarlock K. Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis. Blood Adv. 2023 Oct 10;7(19):5941-5953. doi: 10.1182/bloodadvances.2022008282.
    pmid
    37267439
    type
    DERIVED
  3. citation
    Medeiros BC, Othus M, Fang M, Appelbaum FR, Erba HP. Cytogenetic heterogeneity negatively impacts outcomes in patients with acute myeloid leukemia. Haematologica. 2015 Mar;100(3):331-5. doi: 10.3324/haematol.2014.117267. Epub 2014 Dec 19.
    pmid
    25527568
    type
    DERIVED
  4. citation
    Medeiros BC, Othus M, Estey EH, Fang M, Appelbaum FR. Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia. Br J Haematol. 2014 Jan;164(2):245-50. doi: 10.1111/bjh.12625. Epub 2013 Oct 28.
    pmid
    24383844
    type
    DERIVED
  5. citation
    Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. doi: 10.1182/blood-2013-01-466706. Epub 2013 Apr 16.
    pmid
    23591789
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        </li><li>Another analysis was conducted among patients enrolled in a prospective cooperative group trial, <a href="/clinicaltrials/NCT00085709">SWOG S0106</a> (NCT00085709).[<a href="#cit/section_6.30">30</a>] <div class="pdq-content-list"><ul id="_723"><li>Of the 589 patients treated in the cooperative group trial, 150 (25%) had
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      1. context
        Updated: March 14, 2025
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        March 14, 2025

    Preserved source evidence · Not medical advice