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

NCT ID: NCT00002517

Last Updated: 2010-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 1993-03-31

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

thioguanine

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Principal Investigators

Catherine Behar, MD

Role: STUDY_CHAIR

Hopital Americain

Locations

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

Hopital Universitaire Des Enfants Reine Fabiola

Brussels, , Belgium

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

Clinique de l'Esperance

Montegnée, , Belgium

Centre Hospitalier Regional et Universitaire d'Angers

Angers, , France

CHR de Besancon - Hopital Saint-Jacques

Besançon, , France

CHU de Caen

Caen, , France

CHR de Grenoble - La Tronche

Grenoble, , France

Centre Hospitalier Regional de Lille

Lille, , France

Hopital Debrousse

Lyon, , France

Hopital Arnaud de Villeneuve

Montpellier, , France

CHR Hotel Dieu

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

Hopital Robert Debre

Paris, , France

Institut Curie - Section Medicale

Paris, , France

Hopital Jean Bernard

Poitiers, , France

Hopital Americain

Reims, , France

Hopital Universitaire Hautepierre

Strasbourg, , France

Hopital des Enfants (Purpan Enfants)

Toulouse, , France

Hospital Escolar San Joao

Porto, , Portugal

Countries

Belgium; France; Portugal

References

Brunet AS, Ploton C, Galambrun C, Pondarre C, Pages MP, Bleyzac N, Freydiere AM, Barbe G, Bertrand Y. Low incidence of sepsis due to viridans streptococci in a ten-year retrospective study of pediatric acute myeloid leukemia. Pediatr Blood Cancer. 2006 Nov;47(6):765-72. doi: 10.1002/pbc.20706.

Reference Type: RESULT

PMID: 16333838 (View on PubMed)

Entz-Werle N, Suciu S, van der Werff ten Bosch J, Vilmer E, Bertrand Y, Benoit Y, Margueritte G, Plouvier E, Boutard P, Vandecruys E, Ferster A, Lutz P, Uyttebroeck A, Hoyoux C, Thyss A, Rialland X, Norton L, Pages MP, Philippe N, Otten J, Behar C; EORTC Children Leukemia Group. Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report. Leukemia. 2005 Dec;19(12):2072-81. doi: 10.1038/sj.leu.2403932.

Reference Type: RESULT

PMID: 16136166 (View on PubMed)

Other Identifiers

EORTC-58921

Identifier Type: -

Identifier Source: secondary_id

CDR0000078212

Identifier Type: -

Identifier Source: org_study_id