Back to resultsInternational Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia
Primary Purpose
Leukemia
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
PEG-L-asparaginase
cyclophosphamide
cytarabine
daunorubicin hydrochloride
dexamethasone
doxorubicin hydrochloride
etoposide
ifosfamide
mercaptopurine
methotrexate
prednisone
thioguanine
vincristine sulfate
vindesine
daunoxome
fludarabine
Radiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia
Eligibility 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
Sites / Locations
- The Sydney Children's Hospital, Centre for Children's Cancer and Blood Disorders
- The Children's Hospital at Westmead, Department of Oncology
- Krankenhaus Dornbirn, Abt. für Kinder- und Jugendheilkunde
- Univ.-Kinderklinik Graz, Abt. Pädiatrische Hämato-Onkologie
- Department f. Kinder- u. Jugendheilkunde, Universitätsklinik f. Pädiatrie II
- A.oe. Landeskrankenhaus Klagenfurt, Abt. für Kinder- und Jugendheilkunde
- A.oe. Landeskrankenhaus Leoben, Abt. für Kinder und Jugendliche
- Landes-Kinderklinik Linz, Haematologie/Onkologie
- St. Johanns Spital / Landeskrankenhaus, Salzburg, Kinderspital Abt. Kinder u. Jugendheilkunde
- St. Anna Kinderspital, Zentrum für Kinder- und Jugendheilkunde
- University Hospital Brno, Department of Pediatric Oncology
- University Hospital Hradec Králové, Department of Pediatrics
- University Hospital Olomouc, Department of Pediatrics
- Teaching Hospital Ostrava-Poruba, Department of Pediatrics
- University Hospital Plzeň, Department of Pediatrics
- University Hospital Motol, Department of Pediatric Hematology and Oncology
- Masaryk´s Hospital Ústí nad Labem, Department of Pediatrics
- Regional Hospital České Budějovice, Department of Pediatrics
- Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
- I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
- Klinikum Bayreuth, Kinderklinik
- Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
- Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
- Städtisches Krankenhaus, Kinderklinik
- Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
- Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
- Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
- Klinikum Lippe-Detmold, Kinder- und Jugendmedizin
- Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
- Uni.Klinik Carl Gustav Carus, Klinik f. Kinderheilkunde
- Universitätskinderklinik
- Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
- Universitätsklinikum Erlangen, Kinder- und Jugendmedizin, Abt. für Onkologie/ Hämatologie/Immunologie
- Universitätsklinikum Essen, Kinderklinik, Hämatologie/Onkologie
- Universitäts-Kinderklinik, Klinik für Kinderheilkunde III, Pädiatrische Hämatologie/Onkologie
- Universitäts-Kinderklinik, Haematologie/ Onkologie
- Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
- Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
- Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
- Uniklinikum d. Martin Luther Universität, Halle Wittenberg, Univ.-und Poliklinik für Kinder- und Jugendmedizin
- Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
- Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
- Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
- Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
- Universitätsklinik für, Kinder- und Jugendmedizin, Päd. Hämatologie/ Onkologie
- Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
- Städtisches Klinikum Karlsruhe, Kinderklinik
- Klinikum Kassel, Kinderklinik
- Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
- Städtisches Krankenhaus Kemperhof, Kinderklinik
- Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
- Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
- Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
- Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
- Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
- Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
- Johannes Wesling Klinikum Minden
- Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
- Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
- Cnopf'sche Kinderklinik, Onkologie
- Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
- Universitäts-Kinderklinik
- Asklepios-Klinik, Sankt Augustin GmbH
- HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
- Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
- Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
- Universitäts-Kinderklinik, Abt. Kinderheilkunde II, Hämatologie/Onkologie
- Universitäts-Kinderklinik
- Stadtkrankenhaus, Kinderklinik
- Universitäts-Kinderklinik
- HaEmek Medical Center
- Soroka Medical Center
- Rambam Medical Center
- Bnai-Zion Medical Center
- Hadassah University Medical Center
- Schneider Children Medical Center of Israel
- Dana children hospital
- Sheba Medical Center
- Centro Regionale Oncoematologia Pediatrica Ospedale dei Bambini "G. Salesi" Clinica Pediatrica
- Dipartimento Biomedicina Età Evolutiva U.O Pediatrica I Policlinico
- U.O.C. Pediatria e Patologia Neonatale Ospedale San Martino
- U.O. Pediatrica - OO.RR Bergamo
- Istituto Ortopedico Rizzoli Sez. di chemioterapia dei tumori dell'apparato locomotore
- Oncologia ed Ematologia "Lalla Seràgnoli" Clinica Pediatrica Policlinico Sant'Orsola Malpighi
- Pediatria Ospedale Regionale
- Clinica Pediatrica Oncoematologia pediatrica e TMO Ospedale dei Bambini
- Istituto di Clinica Pediatrica Ospedale Regionale per le Microcitemie
- Divisione Ematologia - Oncologia Pediatrica Clinica Pediatrica
- Unità Operativa di Ematologia ed Oncologia Pediatrica Az. Osp. "Pugliese-Ciaccio"
- Unità Operativa Pediatria Azienda Ospedaliera Annuziata
- Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria Università di Ferrara
- Dipartimento A.I. Oncoematologia Pediatrica e Cure Domiciliari U.O. Oncoematologia Pediatrica Azienda Ospedaliero-Universitaria Meyer
- Dipartimento di Ematologia e Oncologia Pediatrica Instituto " G. Gaslini"
- Ospedale "Vito Fazzi" U.O. di Pediatria
- Clinica Pediatrica II De Marchi
- Unità di Ricerca Clinica Pediatrica HSR TIGET - Istituto Scientifico San Raffaele
- Divisione di Oncologia Pediatrica Ist. Nazionale Studio e Cura Tumori
- Divisione Pediatria "Mariani" Ospedale "Niguarda Ca' Granda"
- U.O. di Ematologia, oncologia e trapianto Azienda Policlinico di Modena
- Clinica Pediatrica dell'Università Milano - Bicocca A.O. San Gerardo - Fondazione MBBM
- Dipartimento di Oncologia A.O. Santobono - Pausilipon
- A.O. "A. Cardarelli", U.O.S. Talassemia pediatrica ed emoglobinopatie pediatriche
- Servizio di Oncologia Pediatrica Dipartimento di Pediatria Seconda Università degli Studi di Napoli
- U.O.C. Pediatria - TIN, Ospedale "Umberto Primo" ASL SA - 1
- S.C.D.U. Azienda Ospedaliera "Maggiore della carità"
- Dipartimento di Pediatria Università di Padova Cattedra Di Oncoematologia Pediatrica
- Oncoematologia Pediatrica Ospedale dei Bambini G. di Cristina
- U.O. di Pediatria e Oncoematologia Pediatrica Az. Osp. Di Parma Ospedali Riuniti
- Oncoematologia Pediatrica IRCCS, Policlinico San Matteo
- S.C. di Oncoematologia Pediatrica con Trapianto di CSE, Ospedale "S.M. della Misericordia" A.O. Perugia
- Ematologia, Ospedale di Muraglia
- U.O. Pediatrica Azienda Ospedaliera San Salvatore
- Dipartimento di Ematologia Ospedale Civile
- Centro di Oncoematologia Pediatrica e Trapianto Midollo Osseo Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
- Centro Integrato di Emato-oncologia e dell'adolescenza A.O. S. Maria degli Angeli - Pordenone e IRCCS Centro di Riferimento Oncologico - Aviano
- Divisione Ematologia Ospedali Riuniti
- U.O Pediatria Ospedale Infermi Azienda USL Rimini
- Ospedale Sant'Eugenio clinica pediatrica Univ. Tor Vergata
- Oncoematologia pediatrica Università "La Sapienza" Roma
- Sezione Ematologia Dipart. di biotecnologie Cellulari ed Ematologia Università "La Sapienza"
- Divisione di Ematologia Pediatrica Ospedale "Bambin Gesù"Istituto di Ricerca Scientifica
- Divisione Oncologia Pediatrica Ospedale "Bambin Gesù"
- Divisione Oncologia Pediatrica Università Cattolica di Roma
- U.O. Oncoematologia Pediatrica Ospedale "Casa Sollievo della Sofferenza"
- Clinica Pediatrica Università
- Dipartimento di Pediatria Ostetricia e Medicina della Riproduzione Università degli Studi di Siena
- Ospedale Infantile Regina Margherita
- Unità Operativa di Pediatria - U.T.I.N. Az.Osp. "Card. G. Panico"
- U.O. Emato-Oncologia Pediatrica Università degli studi di Trieste Ospedale Infantile Burlo Garofolo
- SOS Oncologia Pediatrica Policlinico Universitario
- Clinica Pediatrica Università degli Studi dell'Insubria di Varese Ospedale "Filippo del Ponte"
- U.O.C Oncoematologia Pediatrica Policlinico "G.B: Rossi"
- Ospedale San Bortolo, U.O. di Pediatria e patologia Neonatale
- Kinderklinik, Hämatologie/Onkologie
- Baseler Kinderspital, Hämatologische Poliklinik
- Repartio di Pediatria
- Pädiatrische Klinik, Kinderspital Luzern, Kinderonkologie
- Hämatologie/Onkologie, Ostschweizer Kinderspital, FMH Pädiatrie, Hämatologie
- Kinderspital Zürich, Universitäts-Kinderklinik
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Active Comparator
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Arm Label
R1 control arm
R1 experimental arm
R2 control arm
R2 experimental arm
R-HR control arm
R-HR experimental arm
Arm Description
see detailed protocol description
see detailed protocol description
see detailed protocol description
see detailed protocol description
see detailed protocol description
see detailed protocol description
Outcomes
Primary Outcome Measures
Event-free survival
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
Randomization R2: Disease-free survival from time of randomization
Historical comparison SR: Disease-free survival from start of Protocol M
minimal residual disease (MRD)
Randomization RHR: rate of MRD highly positive patients (MRD ≥ 10-3) at TP2 (week 12)
Secondary Outcome Measures
survival
All randomized and historical comparisons: Survival
treatment-related mortality
All randomized and historical comparisons: treatment-related mortality in induction or CCR (overall and by chemotherapy/SCT)
adverse events
All randomized and historical comparisons: incidence and frequency of adverse events of interest and serious adverse events
event-free survival
Randomization R-HR: Event-free survival from time of randomization
minimal residual disease
"MRD Non-Responders": MRD levels after DNX-FLA
Full Information
NCT ID
NCT01117441
First Posted
May 3, 2010
Last Updated
May 17, 2022
Sponsor
University Hospital Schleswig-Holstein
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany)
1. Study Identification
Unique Protocol Identification Number
NCT01117441
Brief Title
International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia
Official Title
International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Schleswig-Holstein
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany)
4. Oversight
Data Monitoring Committee
Yes
5. 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?
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
R1 control arm
Arm Type
Active Comparator
Arm Description
see detailed protocol description
Arm Title
R1 experimental arm
Arm Type
Experimental
Arm Description
see detailed protocol description
Arm Title
R2 control arm
Arm Type
Active Comparator
Arm Description
see detailed protocol description
Arm Title
R2 experimental arm
Arm Type
Experimental
Arm Description
see detailed protocol description
Arm Title
R-HR control arm
Arm Type
Active Comparator
Arm Description
see detailed protocol description
Arm Title
R-HR experimental arm
Arm Type
Experimental
Arm Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
PEG-L-asparaginase
Other Intervention Name(s)
Oncaspar medac
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
daunorubicin hydrochloride
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
mercaptopurine
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
thioguanine
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
vindesine
Intervention Description
see detailed protocol description
Intervention Type
Drug
Intervention Name(s)
daunoxome
Intervention Description
see detailed protocol description; only given by patients with poor MRD-response during the high risk treatment
Intervention Type
Drug
Intervention Name(s)
fludarabine
Intervention Description
see detailed protocol description; only given by patients with poor MRD-response during the high risk treatment
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Intervention Description
for eligibility for radiotherapy see detailed protocol description
Primary Outcome Measure Information:
Title
Event-free survival
Description
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)
Time Frame
10 years from the start of recruitment
Title
Disease-free survival
Description
Randomization R2: Disease-free survival from time of randomization
Historical comparison SR: Disease-free survival from start of Protocol M
Time Frame
10 years from the start of recruitment
Title
minimal residual disease (MRD)
Description
Randomization RHR: rate of MRD highly positive patients (MRD ≥ 10-3) at TP2 (week 12)
Time Frame
week 12 of treatment
Secondary Outcome Measure Information:
Title
survival
Description
All randomized and historical comparisons: Survival
Time Frame
10 years from the start of recruitment
Title
treatment-related mortality
Description
All randomized and historical comparisons: treatment-related mortality in induction or CCR (overall and by chemotherapy/SCT)
Time Frame
up to 25 months from the diagnosis
Title
adverse events
Description
All randomized and historical comparisons: incidence and frequency of adverse events of interest and serious adverse events
Time Frame
up to 25 months from the diagnosis
Title
event-free survival
Description
Randomization R-HR: Event-free survival from time of randomization
Time Frame
10 years from the start of recruitment
Title
minimal residual disease
Description
"MRD Non-Responders": MRD levels after DNX-FLA
Time Frame
after 24 weeks of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Schrappe, MD PhD
Organizational Affiliation
Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Sydney Children's Hospital, Centre for Children's Cancer and Blood Disorders
City
Randwick
ZIP/Postal Code
NSW 2031
Country
Australia
Facility Name
The Children's Hospital at Westmead, Department of Oncology
City
Westmead
ZIP/Postal Code
NSW 2145
Country
Australia
Facility Name
Krankenhaus Dornbirn, Abt. für Kinder- und Jugendheilkunde
City
Dornbirn
ZIP/Postal Code
6850
Country
Austria
Facility Name
Univ.-Kinderklinik Graz, Abt. Pädiatrische Hämato-Onkologie
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Department f. Kinder- u. Jugendheilkunde, Universitätsklinik f. Pädiatrie II
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
A.oe. Landeskrankenhaus Klagenfurt, Abt. für Kinder- und Jugendheilkunde
City
Klagenfurt
ZIP/Postal Code
9026
Country
Austria
Facility Name
A.oe. Landeskrankenhaus Leoben, Abt. für Kinder und Jugendliche
City
Leoben
ZIP/Postal Code
8700
Country
Austria
Facility Name
Landes-Kinderklinik Linz, Haematologie/Onkologie
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
St. Johanns Spital / Landeskrankenhaus, Salzburg, Kinderspital Abt. Kinder u. Jugendheilkunde
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
St. Anna Kinderspital, Zentrum für Kinder- und Jugendheilkunde
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
University Hospital Brno, Department of Pediatric Oncology
City
Brno
ZIP/Postal Code
662 63
Country
Czechia
Facility Name
University Hospital Hradec Králové, Department of Pediatrics
City
Hradec Králové
ZIP/Postal Code
500 12
Country
Czechia
Facility Name
University Hospital Olomouc, Department of Pediatrics
City
Olomouc
ZIP/Postal Code
770 00
Country
Czechia
Facility Name
Teaching Hospital Ostrava-Poruba, Department of Pediatrics
City
Ostrava-Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
University Hospital Plzeň, Department of Pediatrics
City
Plzeň
ZIP/Postal Code
304 60
Country
Czechia
Facility Name
University Hospital Motol, Department of Pediatric Hematology and Oncology
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Masaryk´s Hospital Ústí nad Labem, Department of Pediatrics
City
Ústí nad Labem
ZIP/Postal Code
401 13
Country
Czechia
Facility Name
Regional Hospital České Budějovice, Department of Pediatrics
City
České Budějovice
ZIP/Postal Code
370 01
Country
Czechia
Facility Name
Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
Facility Name
Klinikum Bayreuth, Kinderklinik
City
Bayreuth
ZIP/Postal Code
95445
Country
Germany
Facility Name
Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Städtisches Krankenhaus, Kinderklinik
City
Braunschweig
ZIP/Postal Code
38118
Country
Germany
Facility Name
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
City
Chemnitz
ZIP/Postal Code
09009
Country
Germany
Facility Name
Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
City
Cottbus
ZIP/Postal Code
03048
Country
Germany
Facility Name
Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
City
Datteln
ZIP/Postal Code
45711
Country
Germany
Facility Name
Klinikum Lippe-Detmold, Kinder- und Jugendmedizin
City
Detmold
ZIP/Postal Code
32756
Country
Germany
Facility Name
Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
City
Dortmund
ZIP/Postal Code
44137
Country
Germany
Facility Name
Uni.Klinik Carl Gustav Carus, Klinik f. Kinderheilkunde
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätskinderklinik
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
City
Erfurt
ZIP/Postal Code
99089
Country
Germany
Facility Name
Universitätsklinikum Erlangen, Kinder- und Jugendmedizin, Abt. für Onkologie/ Hämatologie/Immunologie
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum Essen, Kinderklinik, Hämatologie/Onkologie
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universitäts-Kinderklinik, Klinik für Kinderheilkunde III, Pädiatrische Hämatologie/Onkologie
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitäts-Kinderklinik, Haematologie/ Onkologie
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
City
Gießen
ZIP/Postal Code
35385
Country
Germany
Facility Name
Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
City
Göttingen
ZIP/Postal Code
37099
Country
Germany
Facility Name
Uniklinikum d. Martin Luther Universität, Halle Wittenberg, Univ.-und Poliklinik für Kinder- und Jugendmedizin
City
Halle
ZIP/Postal Code
06120
Country
Germany
Facility Name
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
City
Heilbronn
ZIP/Postal Code
74078
Country
Germany
Facility Name
Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
City
Herdecke
ZIP/Postal Code
58313
Country
Germany
Facility Name
Universitätsklinik für, Kinder- und Jugendmedizin, Päd. Hämatologie/ Onkologie
City
Homburg / Saar
ZIP/Postal Code
66421
Country
Germany
Facility Name
Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
City
Jena
ZIP/Postal Code
7740
Country
Germany
Facility Name
Städtisches Klinikum Karlsruhe, Kinderklinik
City
Karlsruhe
ZIP/Postal Code
76133
Country
Germany
Facility Name
Klinikum Kassel, Kinderklinik
City
Kassel
ZIP/Postal Code
34125
Country
Germany
Facility Name
Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Städtisches Krankenhaus Kemperhof, Kinderklinik
City
Koblenz
ZIP/Postal Code
56073
Country
Germany
Facility Name
Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
City
Köln
ZIP/Postal Code
50735
Country
Germany
Facility Name
Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Johannes Wesling Klinikum Minden
City
Minden
ZIP/Postal Code
32429
Country
Germany
Facility Name
Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
City
München
ZIP/Postal Code
80804
Country
Germany
Facility Name
Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Cnopf'sche Kinderklinik, Onkologie
City
Nürnberg
ZIP/Postal Code
90419
Country
Germany
Facility Name
Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
City
Oldenburg
ZIP/Postal Code
26133
Country
Germany
Facility Name
Universitäts-Kinderklinik
City
Rostock
ZIP/Postal Code
18055
Country
Germany
Facility Name
Asklepios-Klinik, Sankt Augustin GmbH
City
Sankt Augustin
ZIP/Postal Code
53757
Country
Germany
Facility Name
HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
City
Schwerin
ZIP/Postal Code
19049
Country
Germany
Facility Name
Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
City
Stuttgart
ZIP/Postal Code
70176
Country
Germany
Facility Name
Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
City
Trier
ZIP/Postal Code
54290
Country
Germany
Facility Name
Universitäts-Kinderklinik, Abt. Kinderheilkunde II, Hämatologie/Onkologie
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitäts-Kinderklinik
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Facility Name
Stadtkrankenhaus, Kinderklinik
City
Wolfsburg
ZIP/Postal Code
38440
Country
Germany
Facility Name
Universitäts-Kinderklinik
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
HaEmek Medical Center
City
Afula
ZIP/Postal Code
18101
Country
Israel
Facility Name
Soroka Medical Center
City
Beer-Sheva
ZIP/Postal Code
84101
Country
Israel
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Bnai-Zion Medical Center
City
Haifa
ZIP/Postal Code
33394
Country
Israel
Facility Name
Hadassah University Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Schneider Children Medical Center of Israel
City
Petach Tikva
ZIP/Postal Code
49202
Country
Israel
Facility Name
Dana children hospital
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Sheba Medical Center
City
Tel-Hashomer
Country
Israel
Facility Name
Centro Regionale Oncoematologia Pediatrica Ospedale dei Bambini "G. Salesi" Clinica Pediatrica
City
Ancona
ZIP/Postal Code
60123
Country
Italy
Facility Name
Dipartimento Biomedicina Età Evolutiva U.O Pediatrica I Policlinico
City
Bari
ZIP/Postal Code
70124
Country
Italy
Facility Name
U.O.C. Pediatria e Patologia Neonatale Ospedale San Martino
City
Belluno
ZIP/Postal Code
32100
Country
Italy
Facility Name
U.O. Pediatrica - OO.RR Bergamo
City
Bergamo
ZIP/Postal Code
24100
Country
Italy
Facility Name
Istituto Ortopedico Rizzoli Sez. di chemioterapia dei tumori dell'apparato locomotore
City
Bologna
ZIP/Postal Code
40136
Country
Italy
Facility Name
Oncologia ed Ematologia "Lalla Seràgnoli" Clinica Pediatrica Policlinico Sant'Orsola Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Pediatria Ospedale Regionale
City
Bolzano
ZIP/Postal Code
39100
Country
Italy
Facility Name
Clinica Pediatrica Oncoematologia pediatrica e TMO Ospedale dei Bambini
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Istituto di Clinica Pediatrica Ospedale Regionale per le Microcitemie
City
Cagliari
ZIP/Postal Code
09121
Country
Italy
Facility Name
Divisione Ematologia - Oncologia Pediatrica Clinica Pediatrica
City
Catania
ZIP/Postal Code
95123
Country
Italy
Facility Name
Unità Operativa di Ematologia ed Oncologia Pediatrica Az. Osp. "Pugliese-Ciaccio"
City
Catanzaro
ZIP/Postal Code
88100
Country
Italy
Facility Name
Unità Operativa Pediatria Azienda Ospedaliera Annuziata
City
Cosenza
ZIP/Postal Code
87100
Country
Italy
Facility Name
Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria Università di Ferrara
City
Ferrara
ZIP/Postal Code
41100
Country
Italy
Facility Name
Dipartimento A.I. Oncoematologia Pediatrica e Cure Domiciliari U.O. Oncoematologia Pediatrica Azienda Ospedaliero-Universitaria Meyer
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Dipartimento di Ematologia e Oncologia Pediatrica Instituto " G. Gaslini"
City
Genova
ZIP/Postal Code
16148
Country
Italy
Facility Name
Ospedale "Vito Fazzi" U.O. di Pediatria
City
Lecce
ZIP/Postal Code
73100
Country
Italy
Facility Name
Clinica Pediatrica II De Marchi
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Unità di Ricerca Clinica Pediatrica HSR TIGET - Istituto Scientifico San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Divisione di Oncologia Pediatrica Ist. Nazionale Studio e Cura Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Divisione Pediatria "Mariani" Ospedale "Niguarda Ca' Granda"
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
U.O. di Ematologia, oncologia e trapianto Azienda Policlinico di Modena
City
Modena
ZIP/Postal Code
41100
Country
Italy
Facility Name
Clinica Pediatrica dell'Università Milano - Bicocca A.O. San Gerardo - Fondazione MBBM
City
Monza
ZIP/Postal Code
20052
Country
Italy
Facility Name
Dipartimento di Oncologia A.O. Santobono - Pausilipon
City
Napoli
ZIP/Postal Code
80123
Country
Italy
Facility Name
A.O. "A. Cardarelli", U.O.S. Talassemia pediatrica ed emoglobinopatie pediatriche
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Servizio di Oncologia Pediatrica Dipartimento di Pediatria Seconda Università degli Studi di Napoli
City
Napoli
ZIP/Postal Code
80138
Country
Italy
Facility Name
U.O.C. Pediatria - TIN, Ospedale "Umberto Primo" ASL SA - 1
City
Nocera Inferiore
ZIP/Postal Code
84014
Country
Italy
Facility Name
S.C.D.U. Azienda Ospedaliera "Maggiore della carità"
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Dipartimento di Pediatria Università di Padova Cattedra Di Oncoematologia Pediatrica
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Oncoematologia Pediatrica Ospedale dei Bambini G. di Cristina
City
Palermo
ZIP/Postal Code
90134
Country
Italy
Facility Name
U.O. di Pediatria e Oncoematologia Pediatrica Az. Osp. Di Parma Ospedali Riuniti
City
Parma
ZIP/Postal Code
43100
Country
Italy
Facility Name
Oncoematologia Pediatrica IRCCS, Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
S.C. di Oncoematologia Pediatrica con Trapianto di CSE, Ospedale "S.M. della Misericordia" A.O. Perugia
City
Perugia
ZIP/Postal Code
06156
Country
Italy
Facility Name
Ematologia, Ospedale di Muraglia
City
Pesaro
ZIP/Postal Code
61100
Country
Italy
Facility Name
U.O. Pediatrica Azienda Ospedaliera San Salvatore
City
Pesaro
ZIP/Postal Code
61100
Country
Italy
Facility Name
Dipartimento di Ematologia Ospedale Civile
City
Pescara
ZIP/Postal Code
65123
Country
Italy
Facility Name
Centro di Oncoematologia Pediatrica e Trapianto Midollo Osseo Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
Centro Integrato di Emato-oncologia e dell'adolescenza A.O. S. Maria degli Angeli - Pordenone e IRCCS Centro di Riferimento Oncologico - Aviano
City
Pordenone
ZIP/Postal Code
33170
Country
Italy
Facility Name
Divisione Ematologia Ospedali Riuniti
City
Reggio Calabria
ZIP/Postal Code
89100
Country
Italy
Facility Name
U.O Pediatria Ospedale Infermi Azienda USL Rimini
City
Rimini
ZIP/Postal Code
47900
Country
Italy
Facility Name
Ospedale Sant'Eugenio clinica pediatrica Univ. Tor Vergata
City
Roma
ZIP/Postal Code
00144
Country
Italy
Facility Name
Oncoematologia pediatrica Università "La Sapienza" Roma
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Sezione Ematologia Dipart. di biotecnologie Cellulari ed Ematologia Università "La Sapienza"
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Divisione di Ematologia Pediatrica Ospedale "Bambin Gesù"Istituto di Ricerca Scientifica
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Divisione Oncologia Pediatrica Ospedale "Bambin Gesù"
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Divisione Oncologia Pediatrica Università Cattolica di Roma
City
Roma
ZIP/Postal Code
00168
Country
Italy
Facility Name
U.O. Oncoematologia Pediatrica Ospedale "Casa Sollievo della Sofferenza"
City
San Giovanni Rotondo
ZIP/Postal Code
71013
Country
Italy
Facility Name
Clinica Pediatrica Università
City
Sassari
ZIP/Postal Code
07100
Country
Italy
Facility Name
Dipartimento di Pediatria Ostetricia e Medicina della Riproduzione Università degli Studi di Siena
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Ospedale Infantile Regina Margherita
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Unità Operativa di Pediatria - U.T.I.N. Az.Osp. "Card. G. Panico"
City
Tricase
ZIP/Postal Code
73039
Country
Italy
Facility Name
U.O. Emato-Oncologia Pediatrica Università degli studi di Trieste Ospedale Infantile Burlo Garofolo
City
Trieste
ZIP/Postal Code
34137
Country
Italy
Facility Name
SOS Oncologia Pediatrica Policlinico Universitario
City
Udine
ZIP/Postal Code
33100
Country
Italy
Facility Name
Clinica Pediatrica Università degli Studi dell'Insubria di Varese Ospedale "Filippo del Ponte"
City
Varese
ZIP/Postal Code
21100
Country
Italy
Facility Name
U.O.C Oncoematologia Pediatrica Policlinico "G.B: Rossi"
City
Verona
ZIP/Postal Code
37134
Country
Italy
Facility Name
Ospedale San Bortolo, U.O. di Pediatria e patologia Neonatale
City
Vicenza
ZIP/Postal Code
36100
Country
Italy
Facility Name
Kinderklinik, Hämatologie/Onkologie
City
Aarau
ZIP/Postal Code
5000
Country
Switzerland
Facility Name
Baseler Kinderspital, Hämatologische Poliklinik
City
Basel
ZIP/Postal Code
4005
Country
Switzerland
Facility Name
Repartio di Pediatria
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Pädiatrische Klinik, Kinderspital Luzern, Kinderonkologie
City
Luzern
ZIP/Postal Code
6000
Country
Switzerland
Facility Name
Hämatologie/Onkologie, Ostschweizer Kinderspital, FMH Pädiatrie, Hämatologie
City
St. Gallen
ZIP/Postal Code
9006
Country
Switzerland
Facility Name
Kinderspital Zürich, Universitäts-Kinderklinik
City
Zürich
ZIP/Postal Code
8032
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
20154213
Citation
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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, Gohring 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.
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Kroll M, Kaupat-Bleckmann K, Morickel 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.
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International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia
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