Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00430118

Recruitment Status : Completed

First Posted : February 1, 2007

Last Update Posted : May 29, 2013

Sponsor:

Information provided by (Responsible Party):

Martin Schrappe, University of Schleswig-Holstein

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy	Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	4559 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	ALL-BFM 2000 Multi-Center Study for the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia
Study Start Date :	July 2000
Actual Primary Completion Date :	January 2012
Actual Study Completion Date :	January 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Childhood Acute Lymphoblastic Leukemia Lymphosarcoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Induction Prot I/Dexa - reinduction Prot III	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Pred - reinduction Prot III	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Dexa - reinduction Prot II	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Active Comparator: Induction Prot I/Pred - reinduction Prot II	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Dexa - reinduction 2x Prot III	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Pred - reinduction 2x Prot III	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Dexa - reinduction 3 HR courses + 3x Prot III	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Pred - reinduction 3 HR courses + 3x Prot III	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Experimental: Induction Prot I/Dexa - reinduction 6 HR courses + Prot II	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy
Active Comparator: Induction Prot I/Pred - reinduction 6 HR courses + Prot II	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Drug: vindesine Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures :

Efficacy of dexamethasone vs prednisone during the induction phase [ Time Frame: End of Trial ]
Event-free survival (EFS) and overall survival after initial remission in intermediate-risk and high-risk patients [ Time Frame: End of Trial ]
Safety and efficacy of treatment reduction during reintensification in standard-risk patients [ Time Frame: End of Trial ]
EFS after second delayed reintensification in intermediate-risk patients [ Time Frame: End of Trial ]
Outcome after extended reintensification therapy in high-risk patients [ Time Frame: End of Trial ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	1 Year to 18 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed acute lymphoblastic leukemia (ALL)
No secondary ALL

PATIENT CHARACTERISTICS:

No prior disease that would preclude treatment with chemotherapy

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior chemotherapy
More than 4 weeks since prior steroids

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00430118

Show 76 Study Locations

Sponsors and Collaborators

University of Schleswig-Holstein

Investigators

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Study Chair:	Martin Schrappe, MD, PhD	University of Schleswig-Holstein

More Information

Publications of Results:

Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke 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, Schäfer BW, Aricò 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.

Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grümayer R, Möricke A, Aricò 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.

Kox 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.

Schrey D, Borghorst S, Lanvers-Kaminsky C, Hempel G, Gerss J, Möricke 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.

Dworzak MN, Schumich A, Printz D, Pötschger 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.

Flohr T, Schrauder A, Cazzaniga G, Panzer-Grümayer R, van der Velden V, Fischer S, Stanulla M, Basso G, Niggli FK, Schäfer 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.

Other Publications:

Attarbaschi A, Mann G, Panzer-Grümayer R, Röttgers S, Steiner M, König M, Csinady E, Dworzak MN, Seidel M, Janousek D, Möricke 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zuna J, Moericke A, Arens M, Koehler R, Panzer-Grümayer 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.

Möricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Aricò 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, Rössig 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.

Cario G, Rhein P, Mitlöhner 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.

Dörge P, Meissner B, Zimmermann M, Möricke 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.

Zeidler L, Zimmermann M, Möricke A, Meissner B, Bartels D, Tschan C, Schrauder A, Cario G, Goudeva L, Jäger 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.

Willer A, Gerss J, König T, Franke D, Kühnel HJ, Henze G, von Stackelberg A, Möricke 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.

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Responsible Party:	Martin Schrappe, Prof. Dr. med., University of Schleswig-Holstein
ClinicalTrials.gov Identifier:	NCT00430118 History of Changes
Other Study ID Numbers:	CDR0000528029 ALL-BFM-2000 EU-20682
First Posted:	February 1, 2007 Key Record Dates
Last Update Posted:	May 29, 2013
Last Verified:	May 2013

Keywords provided by Martin Schrappe, University of Schleswig-Holstein:


T-cell childhood acute lymphoblastic leukemia recurrent childhood acute lymphoblastic leukemia untreated childhood acute lymphoblastic leukemia B-cell childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:

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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Dexamethasone Prednisone Cyclophosphamide Doxorubicin Methotrexate Etoposide	Cytarabine Vincristine Ifosfamide Liposomal doxorubicin Daunorubicin Asparaginase Mercaptopurine Thioguanine Vindesine Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents

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