Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome

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: NCT00002517
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 22, 2010
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which regimen of combination chemotherapy is more effective for acute myeloid leukemia or myelodysplastic syndrome.

PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating children who have newly diagnosed acute myeloid leukemia or myelodysplastic syndrome.

Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndromes Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: etoposide Drug: idarubicin Drug: mitoxantrone hydrochloride Drug: thioguanine Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy Phase 3

Detailed Description:


  • Compare the efficacy of idarubicin vs mitoxantrone in induction and first intensification in terms of achieving and maintaining complete remissions in children with acute myeloid leukemia or myelodysplastic syndrome.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and disease type (de novo acute myeloid leukemia (AML) vs AML secondary to myelodysplastic syndrome (MDS) vs MDS).

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

    • Arm I: Patients receive cytarabine (ARA-C) IV continuously on days 1 and 2 and then IV over 30 minutes every 12 hours on days 3-8, mitoxantrone IV on days 3-5, etoposide (VP-16) IV over 1 hour on days 6-8, and ARA-C intrathecally (IT) on days 1 and 8.
    • Arm II: Patients receive ARA-C and VP-16 as in arm I and idarubicin IV on days 3-5.

Patients on both arms with CNS disease at presentation receive ARA-C IT every 3 days until the CSF clears and then weekly until the first intensification. After induction, patients on both arms proceed to first intensification, regardless of response.

  • First intensification: When blood counts recover and within 40 days after initiating induction, patients are randomized to 1 of 2 treatment arms.

    • Arm III: Patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-3 (if allogeneic bone marrow transplantation (BMT) is planned) or days 1-4 (if allogeneic BMT is not planned) and mitoxantrone IV on days 7-9.
    • Arm IV: Patients receive high-dose ARA-C as in arm III and idarubicin IV on days 7-9.
  • Patients who achieve complete remission (CR) after first intensification and have an HLA-identical, chronic myelomonocytic leukemia-nonreactive, sibling donor undergo allogeneic BMT. Patients who achieve CR after intensification and have no suitable donor receive intensive chemotherapy as defined below. All patients with chloroma at presentation undergo local radiotherapy beginning after final intensification.
  • Second intensification: When blood counts recover, patients receive daunorubicin IV continuously, ARA-C IV continuously, VP-16 IV continuously, oral thioguanine, and oral dexamethasone on days 1-4 and 11-14 and ARA-C IT on days 1, 4, 11, and 14.
  • Third intensification: When blood counts recover, patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-3 and VP-16 IV over 1 hour on days 2-5. When blood counts recover, autologous bone marrow is harvested in the event of subsequent relapse.
  • Maintenance: When blood counts recover, patients receive oral thioguanine daily and ARA-C subcutaneously 4 days a month for 1 year.

PROJECTED ACCRUAL: A total of 310 patients will be accrued for this study within 5 years.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Study Start Date : March 1993
Actual Primary Completion Date : May 2010

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Ages Eligible for Study:   up to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Newly diagnosed acute myeloid leukemia (AML) based on the cytological, cytochemical, and immunological criteria of the FAB classification

    • Must meet 1 of the following criteria:

      • More than 30% blasts in marrow (calculation based on the total number of nucleated cells except lymphocytes and plasmocytes)
      • Presence of granulocytic sarcoma (chloroma)
    • Disease must be associated with at least 1 of the following:

      • More than 3% myeloperoxidase- or Sudan black-positive blasts
      • More than 3% platelet peroxidase-positive blasts
      • More than 20% esterase-positive blasts
      • Immunological markers compatible with a myeloid differentiation, including 1 of the following criteria:

        • Blasts positive for myeloid-associated antigen and negative for B- or T-lymphocyte antigens
        • Blasts positive for at least 2 myeloid antigens (except CD3 and CD8)
      • A cytogenetic abnormality associated with AML OR
  • Newly diagnosed myelodysplastic syndrome (MDS) based on the cytological and cytochemical criteria of the FAB classification

    • Eligible subtypes:

      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation
      • Chronic myelomonocytic leukemia
  • No promyelocytic leukemia (M3 or M3v) treated with tretinoin (protocol EORTC-06915)
  • No AML secondary to hematologic or malignant disease other than MDS
  • Registration must occur within 48 hours of diagnosis



  • Under 15

Performance status:

  • Not specified

Life expectancy:

  • Not specified


  • See Disease Characteristics
  • No uncontrolled bleeding disorder


  • Not specified


  • No renal failure


  • No congenital heart disease


  • No encephalopathy
  • No genetic disorders
  • No uncontrolled infection


Biologic therapy:

  • Not specified


  • Not specified

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified


  • No prior antileukemic therapy

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): NCT00002517

Algemeen Ziekenhuis Middelheim
Antwerp, Belgium, 2020
Hopital Universitaire Des Enfants Reine Fabiola
Brussels, Belgium, 1020
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Centre Hospitalier Regional de la Citadelle
Liege, Belgium, 4000
Clinique de l'Esperance
Montegnee, Belgium, 4420
Centre Hospitalier Regional et Universitaire d'Angers
Angers, France, 49033
CHR de Besancon - Hopital Saint-Jacques
Besancon, France, 25030
CHU de Caen
Caen, France, 14033
CHR de Grenoble - La Tronche
Grenoble, France, 38043
Centre Hospitalier Regional de Lille
Lille, France, 59037
Hopital Debrousse
Lyon, France, 69322
Hopital Arnaud de Villeneuve
Montpellier, France, 34295
CHR Hotel Dieu
Nantes, France, 44093
Centre Antoine Lacassagne
Nice, France, 06189
Hopital Robert Debre
Paris, France, 75019
Institut Curie - Section Medicale
Paris, France, 75248
Hopital Jean Bernard
Poitiers, France, 86021
Hopital Americain
Reims, France, 51092
Hopital Universitaire Hautepierre
Strasbourg, France, 67098
Hopital des Enfants (Purpan Enfants)
Toulouse, France, 31026
Hospital Escolar San Joao
Porto, Portugal, 4200
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Study Chair: Catherine Behar, MD Hopital Americain

Publications of Results: Identifier: NCT00002517     History of Changes
Other Study ID Numbers: CDR0000078212
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 22, 2010
Last Verified: December 2002

Keywords provided by National Cancer Institute (NCI):
childhood myelodysplastic syndromes
untreated childhood acute myeloid leukemia and other myeloid malignancies
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute monocytic leukemia (M5b)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
childhood acute minimally differentiated myeloid leukemia (M0)

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal