Therapy-Optimization Trial for the Treatment of Acute Myeloid Leukemias (AML) in Children and Adolescents

NCT00111345 | Unknown Phase 2 DMC

• 2 other identifiers: BfArM 4022064DKH 50-2728
• Study Type: interventional
• Target: 550
• Locations: 1 country
• Sites: 1

Brief Summary

Due to progressive therapy intensification in the four consecutive studies AML-BFM 78, 83, 93 and 98, prognosis for children with acute myeloid leukemia (AML) has improved steadily. In spite of the intensified therapy, rates of morbidity and mortality have remained unchanged or have even decreased. Against the background that about 40% of the patients still die from immediate causes of an underlying disease relapse or of nonresponse, it seems to be justifiable to intensify therapy - especially for high-risk patients - which on its parts will require an optimization of supportive measures. As the present risk stratification into standard- (SR) and high-risk (HR) patients has proved effective, we will pursue the risk-adapted therapy strategy. The aim of the study is to improve prognosis in children with AML by intensification of cytostatic therapy and to evaluate by randomisation the equivalence of a prophylactic central nervous system (CNS) irradiation with a total dose of 18 Gy versus 12 Gy.

Conditions

Myeloid Leukemia

Keywords

Acute; myeloid; leukemia; Acute myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• Event-free and absolute survival from the date of diagnosis concerning objective 1 and from the date of randomisation concerning objective 2

  5 years

• Concerning objective 3: Disease-free survival from the date of randomisation

  5 years

Secondary Outcomes (1)

• Cardiotoxicity

  5 years

Study Arms (4)

1

EXPERIMENTAL

Daunoxome, standard risk

Drug: liposomal daunorubicin

2

ACTIVE COMPARATOR

Idarubicin, standard risk

Drug: Anthracyclines

3

EXPERIMENTAL

Daunoxome, high-risk, 2-CDA

Drug: 2-CDA

4

ACTIVE COMPARATOR

Idarubicin, high-risk, nothing

Drug: AI

Interventions

Anthracyclines DRUG

3x12 mg/qm

Also known as: Idarubicin

2

liposomal daunorubicin DRUG

3x80 mg/qm

Also known as: Daunoxome

1

2-CDA DRUG

2x6 mg/qm

Also known as: Cladribine

3

AI DRUG

AI

4

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age from \>0 to \</=18 years
• De novo AML, including children with Down syndrome, primary myelosarcomas or acute mixed lineage leukemia/biphenotypic leukemia (predominantly myeloid)
• Admission to one of the member hospitals in Germany participating in the study AML-BFM 2004

You may not qualify if:

• Children with pre-existing syndromes (except Down syndrome)
• AML as secondary malignancy
• Accompanying diseases which do not allow therapy according to the protocol
• Pre-treatment for more than 14 days with another intensive induction therapy

Sponsors & Collaborators

• University Hospital Muenster: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator

Study Sites (1)

University Children's Hospital Muenster, Department of Paediatric Haematology and Oncology

Münster, North Rhine-Westphalia, D-48129, Germany

Location

Related Publications (7)

• Steidel E, Orhan E, Rasche M, Pigazzi M, Tregnago C, Hoffmeister LM, Walter C, Dworzak M, Muhlegger N, von Neuhoff N, Locatelli F, Reinhardt D, Schneider M. Prognostic Value of Molecular Genetic Measurable Residual Disease (MRD) Monitoring in Pediatric Acute Myeloid Leukemia Expressing KMT2A::MLLT10. Eur J Haematol. 2025 Nov;115(5):493-504. doi: 10.1111/ejh.70019. Epub 2025 Aug 13.

  PMID: 40803346 DERIVED

• Tramsen L, Salzmann-Manrique E, Bochennek K, Klingebiel T, Reinhardt D, Creutzig U, Sung L, Lehrnbecher T. Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial. J Clin Oncol. 2016 Aug 10;34(23):2776-83. doi: 10.1200/JCO.2016.66.7881. Epub 2016 Jun 6.

  PMID: 27269945 DERIVED

• Hassler A, Bochennek K, Gilfert J, Perner C, Schoning S, Creutzig U, Reinhardt D, Lehrnbecher T. Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004. Pediatr Blood Cancer. 2016 Jun;63(6):1070-4. doi: 10.1002/pbc.25917. Epub 2016 Jan 27.

  PMID: 26814618 DERIVED

• Creutzig U, Zimmermann M, Bourquin JP, Dworzak MN, Fleischhack G, Graf N, Klingebiel T, Kremens B, Lehrnbecher T, von Neuhoff C, Ritter J, Sander A, Schrauder A, von Stackelberg A, Stary J, Reinhardt D. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013 Jul 4;122(1):37-43. doi: 10.1182/blood-2013-02-484097. Epub 2013 May 23.

  PMID: 23704089 DERIVED

• Creutzig U, Zimmermann M, Bourquin JP, Dworzak MN, Fleischhack G, von Neuhoff C, Sander A, Schrauder A, von Stackelberg A, Ritter J, Stary J, Reinhardt D. CNS irradiation in pediatric acute myleoid leukemia: equal results by 12 or 18 Gy in studies AML-BFM98 and 2004. Pediatr Blood Cancer. 2011 Dec 1;57(6):986-92. doi: 10.1002/pbc.22955. Epub 2011 Apr 7.

  PMID: 21480469 DERIVED

• Klusmann JH, Creutzig U, Zimmermann M, Dworzak M, Jorch N, Langebrake C, Pekrun A, Macakova-Reinhardt K, Reinhardt D. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood. 2008 Mar 15;111(6):2991-8. doi: 10.1182/blood-2007-10-118810. Epub 2008 Jan 8.

  PMID: 18182574 DERIVED

• Meyer LH, Queudeville M, Eckhoff SM, Creutzig U, Reinhardt D, Karawajew L, Ludwig WD, Stahnke K, Debatin KM. Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML. Blood. 2008 Mar 1;111(5):2899-903. doi: 10.1182/blood-2007-08-109058. Epub 2007 Dec 14.

  PMID: 18083847 DERIVED

Related Links

• Click here for more information about this study: Multicenter Therapy-Optimization Trial AML-BFM 2004 for the Treatment of Acute Myeloid Leukemias in Children and Adolescents

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute

Interventions

Anthracyclines; Idarubicin; Daunorubicin; Cladribine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Ursula Creutzig, Prof. Dr. med.

  Medical School Hannover

  PRINCIPAL INVESTIGATOR

• Dirk Reinhardt, Prof. Dr. med.

  Medical School Hanover

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2005
• First Posted: May 20, 2005
• Study Start: March 1, 2004
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2017
• Last Updated: May 23, 2012

Record last verified: 2012-03

Locations

DE (1)