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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002517
• Other study ID #: CDR0000078212
• Secondary ID: EORTC-58921
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 19, 2010
• Start date: March 1993

Study information

• Verified date: December 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 14 Years

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• cytarabine

• daunorubicin hydrochloride

• dexamethasone

• etoposide

• idarubicin

• mitoxantrone hydrochloride

• thioguanine

Procedure:
• allogeneic bone marrow transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Hopital Universitaire Des Enfants Reine Fabiola	Brussels
Belgium	Universitair Ziekenhuis Gent	Ghent
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Centre Hospitalier Regional de la Citadelle	Liege
Belgium	Clinique de l'Esperance	Montegnee
France	Centre Hospitalier Regional et Universitaire d'Angers	Angers
France	CHR de Besancon - Hopital Saint-Jacques	Besancon
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
Portugal	Hospital Escolar San Joao	Porto

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Portugal, 

References & Publications (2)

Brunet AS, Ploton C, Galambrun C, Pondarré C, Pages MP, Bleyzac N, Freydière AM, Barbé 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 No — View Citation

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 — View Citation