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

Phase 3
Completed
Conditions
Leukemia
Myelodysplastic Syndromes
Registration Number
NCT00002517
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (23)

Centre Hospitalier Regional et Universitaire d'Angers

🇫🇷

Angers, France

Algemeen Ziekenhuis Middelheim

🇧🇪

Antwerp, Belgium

Hopital Universitaire Des Enfants Reine Fabiola

🇧🇪

Brussels, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Ghent, Belgium

CHR de Grenoble - La Tronche

🇫🇷

Grenoble, France

CHU de Caen

🇫🇷

Caen, France

Academisch Ziekenhuis der Vrije Universiteit Brussel

🇧🇪

Brussels, Belgium

Centre Hospitalier Regional de la Citadelle

🇧🇪

Liege, Belgium

U.Z. Gasthuisberg

🇧🇪

Leuven, Belgium

Clinique de l'Esperance

🇧🇪

Montegnee, Belgium

CHR de Besancon - Hopital Saint-Jacques

🇫🇷

Besancon, France

Centre Hospitalier Regional de Lille

🇫🇷

Lille, France

Hopital Arnaud de Villeneuve

🇫🇷

Montpellier, France

CHR Hotel Dieu

🇫🇷

Nantes, France

Hopital Debrousse

🇫🇷

Lyon, France

Centre Antoine Lacassagne

🇫🇷

Nice, France

Hopital Robert Debre

🇫🇷

Paris, France

Hopital Jean Bernard

🇫🇷

Poitiers, France

Institut Curie - Section Medicale

🇫🇷

Paris, France

Hopital des Enfants (Purpan Enfants)

🇫🇷

Toulouse, France

Hopital Americain

🇫🇷

Reims, France

Hopital Universitaire Hautepierre

🇫🇷

Strasbourg, France

Hospital Escolar San Joao

🇵🇹

Porto, Portugal

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