Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia
ALL-BFM 2000 Multi-Center Study for the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia
3 other identifiers
interventional
4,559
3 countries
76
Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia. PURPOSE: Thisphase III trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with acute lymphoblastic leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 leukemia
Started Jul 2000
Longer than P75 for phase_3 leukemia
76 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2000
CompletedFirst Submitted
Initial submission to the registry
January 30, 2007
CompletedFirst Posted
Study publicly available on registry
February 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2012
CompletedMay 29, 2013
May 1, 2013
11.5 years
January 30, 2007
May 28, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Efficacy of dexamethasone vs prednisone during the induction phase
End of Trial
Event-free survival (EFS) and overall survival after initial remission in intermediate-risk and high-risk patients
End of Trial
Safety and efficacy of treatment reduction during reintensification in standard-risk patients
End of Trial
EFS after second delayed reintensification in intermediate-risk patients
End of Trial
Outcome after extended reintensification therapy in high-risk patients
End of Trial
Study Arms (10)
Induction Prot I/Dexa - reinduction Prot III
EXPERIMENTALInduction Prot I/Pred - reinduction Prot III
EXPERIMENTALInduction Prot I/Dexa - reinduction Prot II
EXPERIMENTALInduction Prot I/Pred - reinduction Prot II
ACTIVE COMPARATORInduction Prot I/Dexa - reinduction 2x Prot III
EXPERIMENTALInduction Prot I/Pred - reinduction 2x Prot III
EXPERIMENTALInduction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III
EXPERIMENTALInduction Prot I/Pred - reinduction 3 HR courses + 3x Prot III
EXPERIMENTALInduction Prot I/Dexa - reinduction 6 HR courses + Prot II
EXPERIMENTALInduction Prot I/Pred - reinduction 6 HR courses + Prot II
ACTIVE COMPARATORInterventions
Eligibility Criteria
Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.
Sponsors & Collaborators
Study Sites (76)
Krankenhaus Dornbirn
Dornbirn, A-6850, Austria
Landeskrankenhaus Feldkirch
Feldkirch-Tisis, A-6807, Austria
Universitaet Kinderklinik
Graz, 8036, Austria
Innsbruck Universitaetsklinik
Innsbruck, A-6020, Austria
Landeskrankenhaus Klagenfurt
Klagenfurt, 9026, Austria
LKH Leoben
Leoben, A-8700, Austria
A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung
Linz, 4010, Austria
Landes-Kinderkrankenhaus
Linz, A-4020, Austria
St. Johanns-Spital
Salzburg, A-5020, Austria
St. Anna Children's Hospital
Vienna, A-1090, Austria
Kinderklinik - Universitaetsklinikum Aachen
Aachen, D-52074, Germany
Klinikum Augsburg
Augsburg, DOH-86156, Germany
Caritas-Krankenhaus Bad Mergentheim
Bad Mergentheim, D-97980, Germany
Klinikum Bayreuth
Bayreuth, D-95445, Germany
Helios Klinikum Berlin
Berlin, 13125, Germany
Charite University Hospital - Campus Virchow Klinikum
Berlin, D-13353, Germany
Kinderklinik der Universitaet Bonn
Bonn, D-53113, Germany
Staedtisches Klinikum - Howedestrase
Braunschweig, 38118, Germany
Klinikum Chemnitz gGmbH
Chemnitz, D-09116, Germany
Klinikum Coburg
Coburg, 96450, Germany
Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl
Cologne, D-50735, Germany
Children's Hospital
Cologne, D-50924, Germany
Carl - Thiem - Klinkum Cottbus
Cottbus, D-03048, Germany
Vestische Kinderklinik Universitaetsklinik Witten/Herdecke
Datteln, 45711, Germany
Klinikum Lippe - Detmold
Detmold, D-32756, Germany
Klinikum Dortmund
Dortmund, D-44137, Germany
Universitatsklinikum Carl Gustav Carus
Dresden, D-01307, Germany
Klinikum Duisburg
Duisburg, D-47055, Germany
Helios Klinikum Erfurt
Erfurt, 99089, Germany
Universitaets - Kinderklinik
Erlangen, 91054, Germany
Universitaetsklinikum Essen
Essen, D-45147, Germany
Klinikum der J.W. Goethe Universitaet
Frankfurt, D-60590, Germany
Universitaetskinderklinik - Universitaetsklinikum Freiburg
Freiburg im Breisgau, D-79106, Germany
Kinderklinik
Giessen, D-35385, Germany
Universitaetsklinikum Goettingen
Göttingen, D-37075, Germany
Universitaetsklinikum Halle
Halle, D-06097, Germany
Medizinische Hochschule Hannover
Hanover, D-30625, Germany
Universitaets-Kinderklinik Heidelberg
Heidelberg, D-69120, Germany
SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen
Heilbronn, D-74064, Germany
Gemeinschaftskrankenhaus
Herdecke, 58313, Germany
Universitaetsklinikum des Saarlandes
Homburg, 66421, Germany
Universitaets - Kinderklinik
Jena, D-07745, Germany
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, 76133, Germany
Klinikum Kassel
Kassel, D-34125, Germany
University Hospital Schleswig-Holstein - Kiel Campus
Kiel, D-24105, Germany
Klinikum Kemperhof Koblenz
Koblenz, D-56065, Germany
St. Annastift Krankenhaus
Ludwigshafen, 67065, Germany
Universitaets - Kinderklinik - Luebeck
Lübeck, D-23538, Germany
Universitatsklinikum der MA
Magdeburg, 39120, Germany
Staedtisches Klinik - Kinderklinik
Mannheim, D-68167, Germany
Universitaetsklinikum Giessen und Marburg GmbH - Marburg
Marburg, D-35043, Germany
Klinikum Minden
Minden, D-32423, Germany
Krankenhaus Muenchen Schwabing
Munich, 80804, Germany
Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster
Münster, D-48149, Germany
Kinderklinik Kohlhof
Neunkirchen, D-66539, Germany
Cnopf'sche Kinderklinik
Nuremberg, 90419, Germany
Klinikum Oldenburg
Oldenburg, 26133, Germany
Kinderklinik - Universitaetsklinikum Rostock
Rostock, D-18057, Germany
Saarbrucker Winterbergkliniken
Saarbrücken, 66119, Germany
Johanniter-Kinderklinik
Sankt Augustin, 53757, Germany
Klinikum Schwerin
Schwerin, D-19049, Germany
Kinderklink Siegen Deutsches Rotes Kreuz
Siegen, D-57072, Germany
Olgahospital
Stuttgart, D-70176, Germany
Krankenanstalt Mutterhaus der Borromaerinnen
Trier, D-54290, Germany
Universitaetsklinikum Tuebingen
Tübingen, D-72076, Germany
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, D-89075, Germany
St. Marienhospital - Vechta
Vechta, D-49377, Germany
Reinhard-Nieter-Krankenhaus
Wilhelmshaven, D-26389, Germany
Klinikum der Stadt Wolfsburg
Wolfsburg, D-38440, Germany
Universitaets - Kinderklinik Wuerzburg
Würzburg, D-97080, Germany
Kantonsspital Aarau
Aarau, CH-5001, Switzerland
Universitaets-Kinderspital beider Basel
Basel, CH-4005, Switzerland
Ospedale "la Carita", Locarno
Locarno, 6600, Switzerland
Kinderspital Luzern
Lucerne, CH-6000, Switzerland
Ostschweizer Kinderspital
Sankt Gallen, CH-9006, Switzerland
University Children's Hospital
Zurich, CH-8032, Switzerland
Related Publications (16)
Attarbaschi A, Mann G, Panzer-Grumayer R, Rottgers S, Steiner M, Konig M, Csinady E, Dworzak MN, Seidel M, Janousek D, Moricke A, Reichelt C, Harbott J, Schrappe M, Gadner H, Haas OA. Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin-Frankfurt-Munster (ALL-BFM) trials. J Clin Oncol. 2008 Jun 20;26(18):3046-50. doi: 10.1200/JCO.2008.16.1117.
PMID: 18565891BACKGROUNDSchrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grumayer R, Moricke A, Parasole R, Zimmermann M, Dworzak M, Buldini B, Reiter A, Basso G, Klingebiel T, Messina C, Ratei R, Cazzaniga G, Koehler R, Locatelli F, Schafer BW, Arico M, Welte K, van Dongen JJ, Gadner H, Biondi A, Conter V. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011 Aug 25;118(8):2077-84. doi: 10.1182/blood-2011-03-338707. Epub 2011 Jun 30.
PMID: 21719599RESULTConter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A, Arico M, Zimmermann M, Mann G, De Rossi G, Stanulla M, Locatelli F, Basso G, Niggli F, Barisone E, Henze G, Ludwig WD, Haas OA, Cazzaniga G, Koehler R, Silvestri D, Bradtke J, Parasole R, Beier R, van Dongen JJ, Biondi A, Schrappe M. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010 Apr 22;115(16):3206-14. doi: 10.1182/blood-2009-10-248146. Epub 2010 Feb 12.
PMID: 20154213RESULTKox C, Zimmermann M, Stanulla M, Leible S, Schrappe M, Ludwig WD, Koehler R, Tolle G, Bandapalli OR, Breit S, Muckenthaler MU, Kulozik AE. The favorable effect of activating NOTCH1 receptor mutations on long-term outcome in T-ALL patients treated on the ALL-BFM 2000 protocol can be separated from FBXW7 loss of function. Leukemia. 2010 Dec;24(12):2005-13. doi: 10.1038/leu.2010.203. Epub 2010 Oct 14.
PMID: 20944675RESULTSchrey D, Borghorst S, Lanvers-Kaminsky C, Hempel G, Gerss J, Moricke A, Schrappe M, Boos J. Therapeutic drug monitoring of asparaginase in the ALL-BFM 2000 protocol between 2000 and 2007. Pediatr Blood Cancer. 2010 Jul 1;54(7):952-8. doi: 10.1002/pbc.22417.
PMID: 20108339RESULTDworzak MN, Schumich A, Printz D, Potschger U, Husak Z, Attarbaschi A, Basso G, Gaipa G, Ratei R, Mann G, Gadner H. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008 Nov 15;112(10):3982-8. doi: 10.1182/blood-2008-06-164129. Epub 2008 Sep 9.
PMID: 18780832RESULTFlohr T, Schrauder A, Cazzaniga G, Panzer-Grumayer R, van der Velden V, Fischer S, Stanulla M, Basso G, Niggli FK, Schafer BW, Sutton R, Koehler R, Zimmermann M, Valsecchi MG, Gadner H, Masera G, Schrappe M, van Dongen JJ, Biondi A, Bartram CR; International BFM Study Group (I-BFM-SG). Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia. 2008 Apr;22(4):771-82. doi: 10.1038/leu.2008.5. Epub 2008 Jan 31.
PMID: 18239620RESULTJunk SV, Schaeffeler E, Zimmermann M, Moricke A, Beier R, Schutte P, Fedders B, Alten J, Hinze L, Klein N, Kulozik A, Muckenthaler MU, Koehler R, Borkhardt A, Vijayakrishnan J, Ellinghaus D, Forster M, Franke A, Wintering A, Kratz CP, Schrappe M, Schwab M, Houlston RS, Cario G, Stanulla M. Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group. J Exp Clin Cancer Res. 2023 Jan 13;42(1):21. doi: 10.1186/s13046-022-02585-x.
PMID: 36639636DERIVEDStanulla M, Dagdan E, Zaliova M, Moricke A, Palmi C, Cazzaniga G, Eckert C, Te Kronnie G, Bourquin JP, Bornhauser B, Koehler R, Bartram CR, Ludwig WD, Bleckmann K, Groeneveld-Krentz S, Schewe D, Junk SV, Hinze L, Klein N, Kratz CP, Biondi A, Borkhardt A, Kulozik A, Muckenthaler MU, Basso G, Valsecchi MG, Izraeli S, Petersen BS, Franke A, Dorge P, Steinemann D, Haas OA, Panzer-Grumayer R, Cave H, Houlston RS, Cario G, Schrappe M, Zimmermann M; TRANSCALL Consortium; International BFM Study Group. IKZF1plus Defines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia. J Clin Oncol. 2018 Apr 20;36(12):1240-1249. doi: 10.1200/JCO.2017.74.3617. Epub 2018 Mar 2.
PMID: 29498923DERIVEDSchrappe M, Bleckmann K, Zimmermann M, Biondi A, Moricke A, Locatelli F, Cario G, Rizzari C, Attarbaschi A, Valsecchi MG, Bartram CR, Barisone E, Niggli F, Niemeyer C, Testi AM, Mann G, Ziino O, Schafer B, Panzer-Grumayer R, Beier R, Parasole R, Gohring G, Ludwig WD, Casale F, Schlegel PG, Basso G, Conter V. Reduced-Intensity Delayed Intensification in Standard-Risk Pediatric Acute Lymphoblastic Leukemia Defined by Undetectable Minimal Residual Disease: Results of an International Randomized Trial (AIEOP-BFM ALL 2000). J Clin Oncol. 2018 Jan 20;36(3):244-253. doi: 10.1200/JCO.2017.74.4946. Epub 2017 Nov 17.
PMID: 29148893DERIVEDZuna J, Moericke A, Arens M, Koehler R, Panzer-Grumayer R, Bartram CR, Fischer S, Fronkova E, Zaliova M, Schrauder A, Stanulla M, Zimmermann M, Trka J, Stary J, Attarbaschi A, Mann G, Schrappe M, Cario G. Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia. Br J Haematol. 2016 Jun;173(5):742-8. doi: 10.1111/bjh.13989. Epub 2016 Feb 23.
PMID: 26913693DERIVEDMoricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Arico M, Bartram CR, Attarbaschi A, Silvestri D, Beier R, Basso G, Ratei R, Kulozik AE, Lo Nigro L, Kremens B, Greiner J, Parasole R, Harbott J, Caruso R, von Stackelberg A, Barisone E, Rossig C, Conter V, Schrappe M. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016 Apr 28;127(17):2101-12. doi: 10.1182/blood-2015-09-670729. Epub 2016 Feb 17.
PMID: 26888258DERIVEDCario G, Rhein P, Mitlohner R, Zimmermann M, Bandapalli OR, Romey R, Moericke A, Ludwig WD, Ratei R, Muckenthaler MU, Kulozik AE, Schrappe M, Stanulla M, Karawajew L. High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol. Haematologica. 2014 Jan;99(1):103-10. doi: 10.3324/haematol.2013.090225. Epub 2013 Aug 2.
PMID: 23911702DERIVEDDorge P, Meissner B, Zimmermann M, Moricke A, Schrauder A, Bouquin JP, Schewe D, Harbott J, Teigler-Schlegel A, Ratei R, Ludwig WD, Koehler R, Bartram CR, Schrappe M, Stanulla M, Cario G. IKZF1 deletion is an independent predictor of outcome in pediatric acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol. Haematologica. 2013 Mar;98(3):428-32. doi: 10.3324/haematol.2011.056135. Epub 2012 Aug 8.
PMID: 22875627DERIVEDZeidler L, Zimmermann M, Moricke A, Meissner B, Bartels D, Tschan C, Schrauder A, Cario G, Goudeva L, Jager S, Ratei R, Ludwig WD, Teigler-Schlegel A, Skokowa J, Koehler R, Bartram CR, Riehm H, Schrappe M, Welte K, Stanulla M. Low platelet counts after induction therapy for childhood acute lymphoblastic leukemia are strongly associated with poor early response to treatment as measured by minimal residual disease and are prognostic for treatment outcome. Haematologica. 2012 Mar;97(3):402-9. doi: 10.3324/haematol.2011.045229. Epub 2011 Nov 4.
PMID: 22058224DERIVEDWiller A, Gerss J, Konig T, Franke D, Kuhnel HJ, Henze G, von Stackelberg A, Moricke A, Schrappe M, Boos J, Lanvers-Kaminsky C. Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials. Blood. 2011 Nov 24;118(22):5774-82. doi: 10.1182/blood-2011-07-367904. Epub 2011 Sep 22.
PMID: 21940824DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Martin Schrappe, MD, PhD
University Hospital Schleswig-Holstein
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr. med.
Study Record Dates
First Submitted
January 30, 2007
First Posted
February 1, 2007
Study Start
July 1, 2000
Primary Completion
January 1, 2012
Study Completion
January 1, 2012
Last Updated
May 29, 2013
Record last verified: 2013-05