International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01117441

Recruitment Status : Active, not recruiting

First Posted : May 5, 2010

Last Update Posted : October 20, 2020

Sponsor:

Collaborator:

Deutsche Krebshilfe e.V., Bonn (Germany)

Information provided by (Responsible Party):

Martin Schrappe, University Hospital Schleswig-Holstein

Study Description

Brief Summary:

Rationale/Purpose: 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 (ALL).

This trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with ALL.

Study objectives

Primary study questions:

Non high-risk (non-HR) precursor-B ALL (pB-ALL) patients with TEL/AML1-negative ALL or unknown TEL/AML1 status and flow cytometry minimal residual disease (MRD) in bone marrow on day 15 <0.1% or with TEL/AML1-positive ALL (randomized study question R1): Can the daunorubicin dose in Protocol IA be safely reduced by 50 % with a non-inferior EFS and a reduction of toxicity (treatment-related mortality and AE/SAE in Protocol I)?
Patients with pB-ALL and risk group medium risk (MR) (randomized study question R2): Can the clinical outcome be improved by protracted asparagine depletion achieved through application of intensified PEG-L-asparaginase during reintensification and early maintenance?
High-risk (HR) patients (as identified by day 33 - randomized study question RHR): Can the clinical outcome be improved by protracted exposure to PEG-L-asparaginase during Protocol IB?

Secondary study questions:

Standard risk (SR) patients identified by at least one sensitive marker: Is the clinical outcome comparable to that obtained in SR patients (identified with two sensitive markers) in AIEOP-BFM ALL 2000, or can the outcome even be improved with the use of PEG-L-asparaginase instead of native E. coli L-ASP?
T-ALL non-HR patients: Can the high level of outcome which was obtained for these patients in study AIEOP-BFM ALL 2000 be preserved or even improved with the use of PEG-L-ASP instead of native E. coli L-ASP?
HR patients with persisting high MRD levels despite the use of the HR blocks in the intensified consolidation phase "MRD Non-Responders": Is it possible to improve the outcome and to achieve a further reduction of leukemic cell burden by administration of an innovative treatment schedule (DNX-FLA)?
Patients participating in the randomized asparaginase studies (pB-ALL/MR, HR): Are asparaginase activity and asparaginase antibodies associated with development of allergic reactions, and do they have an effect on the outcome of the patients?
What is the relative value of different methods of MRD monitoring in the definition of alternative stratification systems within a BFM-oriented protocol?

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: PEG-L-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 Drug: daunoxome Drug: fludarabine Radiation: Radiation Therapy	Phase 3

Show detailed description

Detailed Description:

Risk Stratification

T/non-HR: T-ALL in absence of any HR criteria (see below)
pB/non-HR: pB-ALL in absence of any HR criteria (see below).
- SR (polymerase chain reaction(PCR)-MRD-SR (MRD-negative on day 33 and 78) or, if no PCR-MRD result available, FCM d15 < 0.1%)
- MR (no SR)
HR: Prednisone poor-response (≥1000 blast cells/µl in peripheral blood on day 8), blast cells ≥10% in bone marrow on day 15 as measured by FCM, non-remission on day 33, positivity for MLL/AF4 or t(4;11), hypodiploidy (< 45 chromosomes), PCR-MRD-HR (MRD ≥10E-3 on day 78) or PCR-MRD-MR SER (only in pB-ALL, MRD ≥ 10-3 on day 33 and MRD positive at a level of < 10E-3 on day 78)

Chemotherapy

According to the risk group, patients receive the following chemotherapy elements:

T/non-HR: Protocol I, Protocol M, Protocol II and Maintenance pB/non-HR: Protocol I, Protocol M, Protocol II and Maintenance HR: Protocol I, HR-1', HR-2', HR-3', 3x Protocol III, Maintenance Patients of the HR group with PCR-MRD ≥10E-3 after element HR-3' are eligible for treatment with element DNX-FLA.

Protocol I Cytoreductive prephase: Prednisone (PDN) on days 1-7 and one dose of methotrexate (MTX) intrathecal (IT) on day 1 Protocol IA: Prednisone (PDN) on days 8 to 28 (21 days); vincristine (VCR) on days 8, 15, 22, 29 (4 doses); daunorubicin (DNR) on days 8, 15, 22 and 29 (4 doses); pegylated L-asparaginase (PEG-L-ASP) on days 12 and 26; MTX IT on days 12 and 33 and in case of blast cells in cerebrospinal fluid at diagnosis additional IT MTX is given on days 19 and 26.

Protocol IA': Only two doses of DNR on days 8 and 15 given to patients eligible for randomization R1 and randomized into the experimental arm Protocol IA-CPM: additional cyclophosphamide (CPM) on day 10 only in T-ALL patients with prednisone poor-response Protocol IA-Dexa (IAD): Dexamethasone (DXM) instead of PDN is given to all patients with T-ALL without any high-risk criteria as identified by day 8.

Protocol IB: CPM on days 36 and 64; cytarabine (ARA-C) on days 38-41, 45-48, 52-55 and 59-62; 6-mercaptopurine (6-MP) on days 36 to 63 (28 days); MTX IT on day 45 and 59 Protocol IB-ASP+: additional PEG-L-ASP on days 40, 47, 54, and 61 (4 doses) are given to the patients eligible for randomization RHR and randomized into the experimental arm.

Protocol M 6-MP on days 1- 56, high-dose MTX (HD-MTX) on days 8, 22, 36, 50 and MTX IT on days 8, 22, 36 and 50 Protocol II Protocol IIA: DXM on days 1 to 21 (21 days); VCR on days 8, 15, 22, 29 (4 doses); doxorubicine (DOX) on days 8, 15, 22 and 29 (4 doses); PEG-L-ASP on day 8 (1 dose); MTX IT on days 1 and 18 only in patients with initial CNS involvement.

Protocol IIA-ASP+: additional PEG-L-ASP on day 22 for patients eligible for randomization R2 and randomized into the experimental arm.

Protocol IIB: CPM on day 36; ARA-C on days 38-41 and 45-48; thioguanine (TG) on days 36 to 49 (14 days) and MTX IT on days 38 and 45.

Protocol IIB-ASP+: additional PEG-L-ASP on days 36 and 50 for eligible for randomization R2 and randomized into the experimental arm.

Protocol III DXM on days 1-15; VCR on days 1 and 8; DOX on days 1 and 8; PEG-L-ASP on day 1; CPM on day 15; ARA-C on days 17-20 and 24-27; TG on days 15 - 28 and MTX IT on days 17 and 24, also on day 1 in patients with initial CNS involvement HR-1' DXM on days 1-5; VCR on days 1 and 6; HD-MTX on day 1; CPM every 12 hours on days 2-4 (5 doses); HD-ARA-C every 12 hours on day 5 (2 doses); PEG-L-ASP on day 6, MTX IT on day 1 HR-2' DXM on days 1 to 5; VDS on days 1 and 6; HD-MTX on day 1; IFO every 12 hours on days 2-4 (5 doses); DNR on day 5; PEG-L-ASP on day 6; MTX IT on day 1 and 1 in patients with initial CNS involvement also day 5 HR-3' DXM on days 1-5; ARA-C 4 x on days 1-2 in 12 h intervals; etoposide (VP-16) every 12 hours on days 3-5 (5 doses); PEG-L-ASP on day 6; MTX IT on day 1 DNX-FLA Flucytosine (FLU) on days 1-5 (5 doses); HD-ARA-C on days 1 to 5 (5 doses); liposomal daunorubicin (DNX) on days 1, 3 and 5 (3 doses); MTX IT on day 1

Interim/Maintenance (until week 104):

6-MP p.o. daily; MTX p.o. once a week, doses adjusted to white blood cell count; PEG-L-ASP: every second week (6 doses), only for patients eligible for randomization R2 and randomized into the experimental arm; MTX IT every 6 weeks up to a total of 6 doses for the following subgroups (all CNS-negative):

T-ALL (HR or non-HR) with < 2 years of age at start of maintenance,
T-ALL, non-HR and initial WBC < 100 000/μl
pB-ALL with PPR and/or FCM-MRD day 15 ≥ 10 % and/or PCR-MRDMR SER as only HR criteria

Radiotherapy Patients without CNS involvement and

T-ALL/non-HR, WBC ≥ 100 000/μl, and age ≥ 2 years at start of pCRT or
with risk group HR and age ≥ 2 years at start of pCRT except pB-ALL with PPR and/or FCM-MRD day 15 ≥ 10 % and/or PCR-MRD-MR SER as only HR criteria receive preventive cranial radiotherapy with 12 Gy

Patients with CNS involvement receive therapeutic cranial radiotherapy with 18 Gy (age 1 to <2 years 12 Gy).

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	4750 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia
Study Start Date :	June 2010
Estimated Primary Completion Date :	December 2021
Estimated Study Completion Date :	December 2021

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 Lymphoblastic Lymphoma Lymphosarcoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: R1 control arm see detailed protocol description	Drug: PEG-L-asparaginase see detailed protocol description Other Name: Oncaspar medac Drug: cyclophosphamide see detailed protocol description Drug: cytarabine see detailed protocol description Drug: daunorubicin hydrochloride see detailed protocol description Drug: dexamethasone see detailed protocol description Drug: doxorubicin hydrochloride see detailed protocol description Drug: mercaptopurine see detailed protocol description Drug: methotrexate see detailed protocol description Drug: prednisone see detailed protocol description Drug: thioguanine see detailed protocol description Drug: vincristine sulfate see detailed protocol description Radiation: Radiation Therapy for eligibility for radiotherapy see detailed protocol description
Experimental: R1 experimental arm see detailed protocol description	Drug: PEG-L-asparaginase see detailed protocol description Other Name: Oncaspar medac Drug: cyclophosphamide see detailed protocol description Drug: cytarabine see detailed protocol description Drug: daunorubicin hydrochloride see detailed protocol description Drug: dexamethasone see detailed protocol description Drug: doxorubicin hydrochloride see detailed protocol description Drug: mercaptopurine see detailed protocol description Drug: methotrexate see detailed protocol description Drug: prednisone see detailed protocol description Drug: thioguanine see detailed protocol description Drug: vincristine sulfate see detailed protocol description Radiation: Radiation Therapy for eligibility for radiotherapy see detailed protocol description
Active Comparator: R2 control arm see detailed protocol description	Drug: PEG-L-asparaginase see detailed protocol description Other Name: Oncaspar medac Drug: cyclophosphamide see detailed protocol description Drug: cytarabine see detailed protocol description Drug: daunorubicin hydrochloride see detailed protocol description Drug: dexamethasone see detailed protocol description Drug: doxorubicin hydrochloride see detailed protocol description Drug: mercaptopurine see detailed protocol description Drug: methotrexate see detailed protocol description Drug: prednisone see detailed protocol description Drug: thioguanine see detailed protocol description Drug: vincristine sulfate see detailed protocol description Radiation: Radiation Therapy for eligibility for radiotherapy see detailed protocol description
Experimental: R2 experimental arm see detailed protocol description	Drug: PEG-L-asparaginase see detailed protocol description Other Name: Oncaspar medac Drug: cyclophosphamide see detailed protocol description Drug: cytarabine see detailed protocol description Drug: daunorubicin hydrochloride see detailed protocol description Drug: dexamethasone see detailed protocol description Drug: doxorubicin hydrochloride see detailed protocol description Drug: mercaptopurine see detailed protocol description Drug: methotrexate see detailed protocol description Drug: prednisone see detailed protocol description Drug: thioguanine see detailed protocol description Drug: vincristine sulfate see detailed protocol description Radiation: Radiation Therapy for eligibility for radiotherapy see detailed protocol description
Active Comparator: R-HR control arm see detailed protocol description	Drug: PEG-L-asparaginase see detailed protocol description Other Name: Oncaspar medac Drug: cyclophosphamide see detailed protocol description Drug: cytarabine see detailed protocol description Drug: daunorubicin hydrochloride see detailed protocol description Drug: dexamethasone see detailed protocol description Drug: doxorubicin hydrochloride see detailed protocol description Drug: etoposide see detailed protocol description Drug: ifosfamide see detailed protocol description Drug: mercaptopurine see detailed protocol description Drug: methotrexate see detailed protocol description Drug: prednisone see detailed protocol description Drug: thioguanine see detailed protocol description Drug: vincristine sulfate see detailed protocol description Drug: vindesine see detailed protocol description Drug: daunoxome see detailed protocol description; only given by patients with poor MRD-response during the high risk treatment Drug: fludarabine see detailed protocol description; only given by patients with poor MRD-response during the high risk treatment Radiation: Radiation Therapy for eligibility for radiotherapy see detailed protocol description
Experimental: R-HR experimental arm see detailed protocol description	Drug: PEG-L-asparaginase see detailed protocol description Other Name: Oncaspar medac Drug: cyclophosphamide see detailed protocol description Drug: cytarabine see detailed protocol description Drug: daunorubicin hydrochloride see detailed protocol description Drug: dexamethasone see detailed protocol description Drug: doxorubicin hydrochloride see detailed protocol description Drug: etoposide see detailed protocol description Drug: ifosfamide see detailed protocol description Drug: mercaptopurine see detailed protocol description Drug: methotrexate see detailed protocol description Drug: prednisone see detailed protocol description Drug: thioguanine see detailed protocol description Drug: vincristine sulfate see detailed protocol description Drug: vindesine see detailed protocol description Drug: daunoxome see detailed protocol description; only given by patients with poor MRD-response during the high risk treatment Drug: fludarabine see detailed protocol description; only given by patients with poor MRD-response during the high risk treatment Radiation: Radiation Therapy for eligibility for radiotherapy see detailed protocol description

Outcome Measures

Primary Outcome Measures :

Event-free survival [ Time Frame: 10 years from the start of recruitment ]
- Randomization R1: Event-free survival from time of randomization
- Historical comparison non-HR T-ALL: Event-free survival from diagnosis
- Historical comparison "MRD Non-Responders": Event-free survival from start of DNX-FLA (morphological non-response after HR-3' is no event for this study question)
Disease-free survival [ Time Frame: 10 years from the start of recruitment ]
- Randomization R2: Disease-free survival from time of randomization
- Historical comparison SR: Disease-free survival from start of Protocol M
minimal residual disease (MRD) [ Time Frame: week 12 of treatment ]
Randomization RHR: rate of MRD highly positive patients (MRD ≥ 10-3) at TP2 (week 12)

Secondary Outcome Measures :

survival [ Time Frame: 10 years from the start of recruitment ]
All randomized and historical comparisons: Survival
treatment-related mortality [ Time Frame: up to 25 months from the diagnosis ]
All randomized and historical comparisons: treatment-related mortality in induction or CCR (overall and by chemotherapy/SCT)
adverse events [ Time Frame: up to 25 months from the diagnosis ]
All randomized and historical comparisons: incidence and frequency of adverse events of interest and serious adverse events
event-free survival [ Time Frame: 10 years from the start of recruitment ]
Randomization R-HR: Event-free survival from time of randomization
minimal residual disease [ Time Frame: after 24 weeks of treatment ]
"MRD Non-Responders": MRD levels after DNX-FLA

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

Inclusion Criteria:

newly diagnosed acute lymphoblastic leukemia
age ≥ 1 year (> 365 days) and < 18 years old (up to 17 years old and 365 days)
no Ph+ (BCR/ABL or t(9;22)-positive) ALL
no evidence of pregnancy or lactation period
no participation in another clinical study
patient enrolled in a participating center
written informed consent

Exclusion Criteria:

pre-treatment with cytostatic drugs
pre-treatment with cytostatic drugs
steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis
treatment started according to another protocol
underlying diseases that prohibit treatment according to the protocol
ALL diagnosed as second malignancy steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis

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): NCT01117441

Locations

Show 139 study locations

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Australia
The Sydney Children's Hospital, Centre for Children's Cancer and Blood Disorders
Randwick, Australia, NSW 2031
The Children's Hospital at Westmead, Department of Oncology
Westmead, Australia, NSW 2145
Austria
Krankenhaus Dornbirn, Abt. für Kinder- und Jugendheilkunde
Dornbirn, Austria, 6850
Univ.-Kinderklinik Graz, Abt. Pädiatrische Hämato-Onkologie
Graz, Austria, 8036
Department f. Kinder- u. Jugendheilkunde, Universitätsklinik f. Pädiatrie II
Innsbruck, Austria, 6020
A.oe. Landeskrankenhaus Klagenfurt, Abt. für Kinder- und Jugendheilkunde
Klagenfurt, Austria, 9026
A.oe. Landeskrankenhaus Leoben, Abt. für Kinder und Jugendliche
Leoben, Austria, 8700
Landes-Kinderklinik Linz, Haematologie/Onkologie
Linz, Austria, 4020
St. Johanns Spital / Landeskrankenhaus, Salzburg, Kinderspital Abt. Kinder u. Jugendheilkunde
Salzburg, Austria, 5020
St. Anna Kinderspital, Zentrum für Kinder- und Jugendheilkunde
Wien, Austria, 1090
Czechia
University Hospital Brno, Department of Pediatric Oncology
Brno, Czechia, 662 63
University Hospital Hradec Králové, Department of Pediatrics
Hradec Králové, Czechia, 500 12
University Hospital Olomouc, Department of Pediatrics
Olomouc, Czechia, 770 00
Teaching Hospital Ostrava-Poruba, Department of Pediatrics
Ostrava-Poruba, Czechia, 708 52
University Hospital Plzeň, Department of Pediatrics
Plzeň, Czechia, 304 60
University Hospital Motol, Department of Pediatric Hematology and Oncology
Praha 5, Czechia, 150 06
Masaryk´s Hospital Ústí nad Labem, Department of Pediatrics
Ústí nad Labem, Czechia, 401 13
Regional Hospital České Budějovice, Department of Pediatrics
České Budějovice, Czechia, 370 01
Germany
Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
Aachen, Germany, 52074
I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
Augsburg, Germany, 86156
Klinikum Bayreuth, Kinderklinik
Bayreuth, Germany, 95445
Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
Berlin, Germany, 13125
Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
Berlin, Germany, 13353
Städtisches Krankenhaus, Kinderklinik
Braunschweig, Germany, 38118
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
Chemnitz, Germany, 09009
Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
Cottbus, Germany, 03048
Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
Datteln, Germany, 45711
Klinikum Lippe-Detmold, Kinder- und Jugendmedizin
Detmold, Germany, 32756
Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
Dortmund, Germany, 44137
Uni.Klinik Carl Gustav Carus, Klinik f. Kinderheilkunde
Dresden, Germany, 01307
Universitätskinderklinik
Düsseldorf, Germany, 40225
Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
Erfurt, Germany, 99089
Universitätsklinikum Erlangen, Kinder- und Jugendmedizin, Abt. für Onkologie/ Hämatologie/Immunologie
Erlangen, Germany, 91054
Universitätsklinikum Essen, Kinderklinik, Hämatologie/Onkologie
Essen, Germany, 45122
Universitäts-Kinderklinik, Klinik für Kinderheilkunde III, Pädiatrische Hämatologie/Onkologie
Frankfurt, Germany, 60590
Universitäts-Kinderklinik, Haematologie/ Onkologie
Freiburg, Germany, 79106
Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
Gießen, Germany, 35385
Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
Greifswald, Germany, 17475
Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
Göttingen, Germany, 37099
Uniklinikum d. Martin Luther Universität, Halle Wittenberg, Univ.-und Poliklinik für Kinder- und Jugendmedizin
Halle, Germany, 06120
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
Hannover, Germany, 30625
Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
Heidelberg, Germany, 69120
Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
Heilbronn, Germany, 74078
Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
Herdecke, Germany, 58313
Universitätsklinik für, Kinder- und Jugendmedizin, Päd. Hämatologie/ Onkologie
Homburg / Saar, Germany, 66421
Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
Jena, Germany, 7740
Städtisches Klinikum Karlsruhe, Kinderklinik
Karlsruhe, Germany, 76133
Klinikum Kassel, Kinderklinik
Kassel, Germany, 34125
Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
Kiel, Germany, 24105
Städtisches Krankenhaus Kemperhof, Kinderklinik
Koblenz, Germany, 56073
Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
Köln, Germany, 50735
Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
Köln, Germany, 50937
Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
Leipzig, Germany, 04103
Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
Lübeck, Germany, 23538
Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
Magdeburg, Germany, 39120
Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
Mannheim, Germany, 68167
Johannes Wesling Klinikum Minden
Minden, Germany, 32429
Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
München, Germany, 80804
Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
Münster, Germany, 48149
Cnopf'sche Kinderklinik, Onkologie
Nürnberg, Germany, 90419
Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
Oldenburg, Germany, 26133
Universitäts-Kinderklinik
Rostock, Germany, 18055
Asklepios-Klinik, Sankt Augustin GmbH
Sankt Augustin, Germany, 53757
HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
Schwerin, Germany, 19049
Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
Stuttgart, Germany, 70176
Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
Trier, Germany, 54290
Universitäts-Kinderklinik, Abt. Kinderheilkunde II, Hämatologie/Onkologie
Tübingen, Germany, 72076
Universitäts-Kinderklinik
Ulm, Germany, 89075
Stadtkrankenhaus, Kinderklinik
Wolfsburg, Germany, 38440
Universitäts-Kinderklinik
Würzburg, Germany, 97080
Israel
HaEmek Medical Center
Afula, Israel, 18101
Soroka Medical Center
Beer-Sheva, Israel, 84101
Rambam Medical Center
Haifa, Israel, 31096
Bnai-Zion Medical Center
Haifa, Israel, 33394
Hadassah University Medical Center
Jerusalem, Israel, 91120
Schneider Children Medical Center of Israel
Petach Tikva, Israel, 49202
Dana children hospital
Tel-Aviv, Israel, 64239
Sheba Medical Center
Tel-Hashomer, Israel
Italy
Centro Regionale Oncoematologia Pediatrica Ospedale dei Bambini "G. Salesi" Clinica Pediatrica
Ancona, Italy, 60123
Dipartimento Biomedicina Età Evolutiva U.O Pediatrica I Policlinico
Bari, Italy, 70124
U.O.C. Pediatria e Patologia Neonatale Ospedale San Martino
Belluno, Italy, 32100
U.O. Pediatrica - OO.RR Bergamo
Bergamo, Italy, 24100
Istituto Ortopedico Rizzoli Sez. di chemioterapia dei tumori dell'apparato locomotore
Bologna, Italy, 40136
Oncologia ed Ematologia "Lalla Seràgnoli" Clinica Pediatrica Policlinico Sant'Orsola Malpighi
Bologna, Italy, 40138
Pediatria Ospedale Regionale
Bolzano, Italy, 39100
Clinica Pediatrica Oncoematologia pediatrica e TMO Ospedale dei Bambini
Brescia, Italy, 25123
Istituto di Clinica Pediatrica Ospedale Regionale per le Microcitemie
Cagliari, Italy, 09121
Divisione Ematologia - Oncologia Pediatrica Clinica Pediatrica
Catania, Italy, 95123
Unità Operativa di Ematologia ed Oncologia Pediatrica Az. Osp. "Pugliese-Ciaccio"
Catanzaro, Italy, 88100
Unità Operativa Pediatria Azienda Ospedaliera Annuziata
Cosenza, Italy, 87100
Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria Università di Ferrara
Ferrara, Italy, 41100
Dipartimento A.I. Oncoematologia Pediatrica e Cure Domiciliari U.O. Oncoematologia Pediatrica Azienda Ospedaliero-Universitaria Meyer
Firenze, Italy, 50139
Dipartimento di Ematologia e Oncologia Pediatrica Instituto " G. Gaslini"
Genova, Italy, 16148
Ospedale "Vito Fazzi" U.O. di Pediatria
Lecce, Italy, 73100
Clinica Pediatrica II De Marchi
Milano, Italy, 20122
Unità di Ricerca Clinica Pediatrica HSR TIGET - Istituto Scientifico San Raffaele
Milano, Italy, 20132
Divisione di Oncologia Pediatrica Ist. Nazionale Studio e Cura Tumori
Milano, Italy, 20133
Divisione Pediatria "Mariani" Ospedale "Niguarda Ca' Granda"
Milano, Italy, 20162
U.O. di Ematologia, oncologia e trapianto Azienda Policlinico di Modena
Modena, Italy, 41100
Clinica Pediatrica dell'Università Milano - Bicocca A.O. San Gerardo - Fondazione MBBM
Monza, Italy, 20052
Dipartimento di Oncologia A.O. Santobono - Pausilipon
Napoli, Italy, 80123
A.O. "A. Cardarelli", U.O.S. Talassemia pediatrica ed emoglobinopatie pediatriche
Napoli, Italy, 80131
Servizio di Oncologia Pediatrica Dipartimento di Pediatria Seconda Università degli Studi di Napoli
Napoli, Italy, 80138
U.O.C. Pediatria - TIN, Ospedale "Umberto Primo" ASL SA - 1
Nocera Inferiore, Italy, 84014
S.C.D.U. Azienda Ospedaliera "Maggiore della carità"
Novara, Italy, 28100
Dipartimento di Pediatria Università di Padova Cattedra Di Oncoematologia Pediatrica
Padova, Italy, 35128
Oncoematologia Pediatrica Ospedale dei Bambini G. di Cristina
Palermo, Italy, 90134
U.O. di Pediatria e Oncoematologia Pediatrica Az. Osp. Di Parma Ospedali Riuniti
Parma, Italy, 43100
Oncoematologia Pediatrica IRCCS, Policlinico San Matteo
Pavia, Italy, 27100
S.C. di Oncoematologia Pediatrica con Trapianto di CSE, Ospedale "S.M. della Misericordia" A.O. Perugia
Perugia, Italy, 06156
Ematologia, Ospedale di Muraglia
Pesaro, Italy, 61100
U.O. Pediatrica Azienda Ospedaliera San Salvatore
Pesaro, Italy, 61100
Dipartimento di Ematologia Ospedale Civile
Pescara, Italy, 65123
Centro di Oncoematologia Pediatrica e Trapianto Midollo Osseo Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
Pisa, Italy, 56126
Centro Integrato di Emato-oncologia e dell'adolescenza A.O. S. Maria degli Angeli - Pordenone e IRCCS Centro di Riferimento Oncologico - Aviano
Pordenone, Italy, 33170
Divisione Ematologia Ospedali Riuniti
Reggio Calabria, Italy, 89100
U.O Pediatria Ospedale Infermi Azienda USL Rimini
Rimini, Italy, 47900
Ospedale Sant'Eugenio clinica pediatrica Univ. Tor Vergata
Roma, Italy, 00144
Oncoematologia pediatrica Università "La Sapienza" Roma
Roma, Italy, 00161
Sezione Ematologia Dipart. di biotecnologie Cellulari ed Ematologia Università "La Sapienza"
Roma, Italy, 00161
Divisione di Ematologia Pediatrica Ospedale "Bambin Gesù"Istituto di Ricerca Scientifica
Roma, Italy, 00165
Divisione Oncologia Pediatrica Ospedale "Bambin Gesù"
Roma, Italy, 00165
Divisione Oncologia Pediatrica Università Cattolica di Roma
Roma, Italy, 00168
U.O. Oncoematologia Pediatrica Ospedale "Casa Sollievo della Sofferenza"
San Giovanni Rotondo, Italy, 71013
Clinica Pediatrica Università
Sassari, Italy, 07100
Dipartimento di Pediatria Ostetricia e Medicina della Riproduzione Università degli Studi di Siena
Siena, Italy, 53100
Ospedale Infantile Regina Margherita
Torino, Italy, 10126
Unità Operativa di Pediatria - U.T.I.N. Az.Osp. "Card. G. Panico"
Tricase, Italy, 73039
U.O. Emato-Oncologia Pediatrica Università degli studi di Trieste Ospedale Infantile Burlo Garofolo
Trieste, Italy, 34137
SOS Oncologia Pediatrica Policlinico Universitario
Udine, Italy, 33100
Clinica Pediatrica Università degli Studi dell'Insubria di Varese Ospedale "Filippo del Ponte"
Varese, Italy, 21100
U.O.C Oncoematologia Pediatrica Policlinico "G.B: Rossi"
Verona, Italy, 37134
Ospedale San Bortolo, U.O. di Pediatria e patologia Neonatale
Vicenza, Italy, 36100
Switzerland
Kinderklinik, Hämatologie/Onkologie
Aarau, Switzerland, 5000
Baseler Kinderspital, Hämatologische Poliklinik
Basel, Switzerland, 4005
Repartio di Pediatria
Bellinzona, Switzerland, 6500
Pädiatrische Klinik, Kinderspital Luzern, Kinderonkologie
Luzern, Switzerland, 6000
Hämatologie/Onkologie, Ostschweizer Kinderspital, FMH Pädiatrie, Hämatologie
St. Gallen, Switzerland, 9006
Kinderspital Zürich, Universitäts-Kinderklinik
Zürich, Switzerland, 8032

Sponsors and Collaborators

University Hospital Schleswig-Holstein

Deutsche Krebshilfe e.V., Bonn (Germany)

Investigators

Layout table for investigator information

Principal Investigator:	Martin Schrappe, MD PhD	Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel

More Information

Publications:

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.

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.

Möricke A, Zimmermann M, Reiter A, Henze G, Schrauder A, Gadner H, Ludwig WD, Ritter J, Harbott J, Mann G, Klingebiel T, Zintl F, Niemeyer C, Kremens B, Niggli F, Niethammer D, Welte K, Stanulla M, Odenwald E, Riehm H, Schrappe M. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010 Feb;24(2):265-84. doi: 10.1038/leu.2009.257. Epub 2009 Dec 10.

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

Würthwein G, Lanvers-Kaminsky C, Siebel C, Gerß J, Möricke A, Zimmermann M, Stary J, Smisek P, Schrappe M, Rizzari C, Zucchetti M, Hempel G, Wicha SG, Boos J; AIEOP-BFM ALL 2009 Asparaginase Working Party. Population Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia: Treatment Phase Dependency and Predictivity in Case of Missing Data. Eur J Drug Metab Pharmacokinet. 2021 Mar;46(2):289-300. doi: 10.1007/s13318-021-00670-8. Epub 2021 Feb 17.

Tasian SK, Peters C. Targeted therapy or transplantation for paediatric ABL-class Ph-like acute lymphocytic leukaemia? Lancet Haematol. 2020 Dec;7(12):e858-e859. doi: 10.1016/S2352-3026(20)30369-0.

Cario G, Leoni V, Conter V, Attarbaschi A, Zaliova M, Sramkova L, Cazzaniga G, Fazio G, Sutton R, Elitzur S, Izraeli S, Lauten M, Locatelli F, Basso G, Buldini B, Bergmann AK, Lentes J, Steinemann D, Göhring G, Schlegelberger B, Haas OA, Schewe D, Buchmann S, Moericke A, White D, Revesz T, Stanulla M, Mann G, Bodmer N, Arad-Cohen N, Zuna J, Valsecchi MG, Zimmermann M, Schrappe M, Biondi A. Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols. Haematologica. 2020 Jul;105(7):1887-1894. doi: 10.3324/haematol.2019.231720. Epub 2019 Oct 10.

Kroll M, Kaupat-Bleckmann K, Mörickel A, Altenl J, Schewel DM, Stanullal M, Zimmermann M, Schrappe M, Cario G. Methotrexate-associated toxicity in children with Down syndrome and acute lymphoblastic leukemia during consolidation therapy with high dose methotrexate according to ALL-BFM treatment regimen. Haematologica. 2020 Apr;105(4):1013-1020. doi: 10.3324/haematol.2019.224774. Epub 2019 Aug 1.

Würthwein G, Lanvers-Kaminsky C, Hempel G, Gastine S, Möricke A, Schrappe M, Karlsson MO, Boos J. Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar(®) in Children with Acute Lymphoblastic Leukemia. Eur J Drug Metab Pharmacokinet. 2017 Dec;42(6):955-963. doi: 10.1007/s13318-017-0410-5.

Layout table for additonal information

Responsible Party:	Martin Schrappe, Prof. Dr. med., University Hospital Schleswig-Holstein
ClinicalTrials.gov Identifier:	NCT01117441
Other Study ID Numbers:	AIEOP-BFM ALL 2009
First Posted:	May 5, 2010 Key Record Dates
Last Update Posted:	October 20, 2020
Last Verified:	October 2020

Additional relevant MeSH terms:

Layout table for MeSH terms

Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Prednisone Cyclophosphamide Ifosfamide Doxorubicin	Liposomal doxorubicin Methotrexate Fludarabine Etoposide Vincristine Daunorubicin Asparaginase Mercaptopurine Thioguanine Pegaspargase Vindesine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents

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