Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome - Full Text View

Sponsor:	European Organization for Research and Treatment of Cancer - EORTC
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002517

Purpose

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	Intervention	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 III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	IDA VS MTZ IN INDUCTION AND INTENSIFICATION TREATMENT OF AML OR MDS IN CHILDREN, A PHASE III RANDOMIZED STUDY

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Anemia Bone Marrow Transplantation Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Dexamethasone Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Etoposide Dexamethasone acetate Idarubicin hydrochloride Idarubicin Mitoxantrone Mitoxantrone hydrochloride Doxiproct plus Etoposide phosphate Cytarabine Thioguanine Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:	March 1993
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	up to 14 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002517

Locations

Belgium
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
France
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
Institut Curie - Section Medicale
Paris, France, 75248
Hopital Robert Debre
Paris, France, 75019
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
Portugal
Hospital Escolar San Joao
Porto, Portugal, 4200

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer - EORTC

Investigators

Study Chair:

Catherine Behar, MD

Hopital Americain

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

ClinicalTrials.gov Identifier:	NCT00002517 History of Changes
Other Study ID Numbers:	CDR0000078212, EORTC-58921
Study First Received:	November 1, 1999
Last Updated:	June 19, 2010
Health Authority:	United States: Federal Government

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
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Thioguanine
Daunorubicin
Dexamethasone
Etoposide

Idarubicin
Mitoxantrone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012