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

June 19, 2010 updated by: European Organisation for Research and Treatment of Cancer - EORTC

IDA VS MTZ IN INDUCTION AND INTENSIFICATION TREATMENT OF AML OR MDS IN CHILDREN, A PHASE III RANDOMIZED STUDY

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • 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

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 14 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • Under 15

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics
  • No uncontrolled bleeding disorder

Hepatic:

  • Not specified

Renal:

  • No renal failure

Cardiovascular:

  • No congenital heart disease

Other:

  • No encephalopathy
  • No genetic disorders
  • No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Not specified

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Other:

  • No prior antileukemic therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Catherine Behar, MD, Hôpital Américain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1993

Primary Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 22, 2010

Last Update Submitted That Met QC Criteria

June 19, 2010

Last Verified

December 1, 2002

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000078212
  • EORTC-58921

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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