Clinical trial NCT01117441: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia
Lead sponsor: University Hospital Schleswig-Holstein
Sponsor class: OTHER
Collaborators: name: Deutsche Krebshilfe e.V., Bonn (Germany)
First posted: 2010-05-05
Enrollment: 6136
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Event-free survival
timeFrame: 10 years from the start of recruitment
measure: Disease-free survival
timeFrame: 10 years from the start of recruitment
measure: minimal residual disease (MRD)
timeFrame: week 12 of treatment
Secondary outcomes:
measure: survival
timeFrame: 10 years from the start of recruitment
measure: treatment-related mortality
timeFrame: up to 25 months from the diagnosis
measure: adverse events
timeFrame: up to 25 months from the diagnosis
measure: event-free survival
timeFrame: 10 years from the start of recruitment
measure: minimal residual disease
timeFrame: after 24 weeks of treatment
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: The Sydney Children's Hospital, Centre for Children's Cancer and Blood Disorders
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead, Department of Oncology
city: Dornbirn
country: Austria
facility: Krankenhaus Dornbirn, Abt. für Kinder- und Jugendheilkunde
city: Graz
country: Austria
facility: Univ.-Kinderklinik Graz, Abt. Pädiatrische Hämato-Onkologie
city: Innsbruck
country: Austria
facility: Department f. Kinder- u. Jugendheilkunde, Universitätsklinik f. Pädiatrie II
city: Klagenfurt
country: Austria
facility: A.oe. Landeskrankenhaus Klagenfurt, Abt. für Kinder- und Jugendheilkunde
city: Leoben
country: Austria
facility: A.oe. Landeskrankenhaus Leoben, Abt. für Kinder und Jugendliche
city: Linz
country: Austria
facility: Landes-Kinderklinik Linz, Haematologie/Onkologie
city: Salzburg
country: Austria
facility: St. Johanns Spital / Landeskrankenhaus, Salzburg, Kinderspital Abt. Kinder u. Jugendheilkunde
city: Wien
country: Austria
facility: St. Anna Kinderspital, Zentrum für Kinder- und Jugendheilkunde
city: Brno
country: Czechia
facility: University Hospital Brno, Department of Pediatric Oncology
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Králové, Department of Pediatrics
city: Olomouc
country: Czechia
facility: University Hospital Olomouc, Department of Pediatrics
city: Ostrava-Poruba
country: Czechia
facility: Teaching Hospital Ostrava-Poruba, Department of Pediatrics
city: Plzeň
country: Czechia
facility: University Hospital Plzeň, Department of Pediatrics
city: Praha 5
country: Czechia
facility: University Hospital Motol, Department of Pediatric Hematology and Oncology
city: Ústí nad Labem
country: Czechia
facility: Masaryk´s Hospital Ústí nad Labem, Department of Pediatrics
city: České Budějovice
country: Czechia
facility: Regional Hospital České Budějovice, Department of Pediatrics
city: Aachen
country: Germany
facility: Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
city: Augsburg
country: Germany
facility: I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth, Kinderklinik
city: Berlin
country: Germany
facility: Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
city: Berlin
country: Germany
facility: Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
city: Braunschweig
country: Germany
facility: Städtisches Krankenhaus, Kinderklinik
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
city: Datteln
country: Germany
facility: Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
city: Detmold
country: Germany
facility: Klinikum Lippe-Detmold, Kinder- und Jugendmedizin
city: Dortmund
country: Germany
facility: Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
city: Dresden
country: Germany
facility: Uni.Klinik Carl Gustav Carus, Klinik f. Kinderheilkunde
city: Düsseldorf
country: Germany
facility: Universitätskinderklinik
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Kinder- und Jugendmedizin, Abt. für Onkologie/ Hämatologie/Immunologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Kinderklinik, Hämatologie/Onkologie
city: Frankfurt
country: Germany
facility: Universitäts-Kinderklinik, Klinik für Kinderheilkunde III, Pädiatrische Hämatologie/Onkologie
city: Freiburg
country: Germany
facility: Universitäts-Kinderklinik, Haematologie/ Onkologie
city: Gießen
country: Germany
facility: Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
city: Greifswald
country: Germany
facility: Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
city: Göttingen
country: Germany
facility: Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
city: Halle
country: Germany
facility: Uniklinikum d. Martin Luther Universität, Halle Wittenberg, Univ.-und Poliklinik für Kinder- und Jugendmedizin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
city: Heidelberg
country: Germany
facility: Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
city: Heilbronn
country: Germany
facility: Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
city: Herdecke
country: Germany
facility: Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
city: Homburg / Saar
country: Germany
facility: Universitätsklinik für, Kinder- und Jugendmedizin, Päd. Hämatologie/ Onkologie
city: Jena
country: Germany
facility: Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe, Kinderklinik
city: Kassel
country: Germany
facility: Klinikum Kassel, Kinderklinik
city: Kiel
country: Germany
facility: Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
city: Koblenz
country: Germany
facility: Städtisches Krankenhaus Kemperhof, Kinderklinik
city: Köln
country: Germany
facility: Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
city: Köln
country: Germany
facility: Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
city: Leipzig
country: Germany
facility: Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
city: Lübeck
country: Germany
facility: Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
city: Mannheim
country: Germany
facility: Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: München
country: Germany
facility: Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
city: Münster
country: Germany
facility: Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
city: Nürnberg
country: Germany
facility: Cnopf'sche Kinderklinik, Onkologie
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
city: Rostock
country: Germany
facility: Universitäts-Kinderklinik
city: Sankt Augustin
country: Germany
facility: Asklepios-Klinik, Sankt Augustin GmbH
city: Schwerin
country: Germany
facility: HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
city: Stuttgart
country: Germany
facility: Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
city: Trier
country: Germany
facility: Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
city: Tübingen
country: Germany
facility: Universitäts-Kinderklinik, Abt. Kinderheilkunde II, Hämatologie/Onkologie
city: Ulm
country: Germany
facility: Universitäts-Kinderklinik
city: Wolfsburg
country: Germany
facility: Stadtkrankenhaus, Kinderklinik
city: Würzburg
country: Germany
facility: Universitäts-Kinderklinik
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Beer-Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: Bnai-Zion Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Children Medical Center of Israel
city: Tel-Aviv
country: Israel
facility: Dana children hospital
city: Tel-Hashomer
country: Israel
facility: Sheba Medical Center
city: Ancona
country: Italy
facility: Centro Regionale Oncoematologia Pediatrica Ospedale dei Bambini "G. Salesi" Clinica Pediatrica
city: Bari
country: Italy
facility: Dipartimento Biomedicina Età Evolutiva U.O Pediatrica I Policlinico
city: Belluno
country: Italy
facility: U.O.C. Pediatria e Patologia Neonatale Ospedale San Martino
city: Bergamo
country: Italy
facility: U.O. Pediatrica - OO.RR Bergamo
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli Sez. di chemioterapia dei tumori dell'apparato locomotore
city: Bologna
country: Italy
facility: Oncologia ed Ematologia "Lalla Seràgnoli" Clinica Pediatrica Policlinico Sant'Orsola Malpighi
city: Bolzano
country: Italy
facility: Pediatria Ospedale Regionale
city: Brescia
country: Italy
facility: Clinica Pediatrica Oncoematologia pediatrica e TMO Ospedale dei Bambini
city: Cagliari
country: Italy
facility: Istituto di Clinica Pediatrica Ospedale Regionale per le Microcitemie
city: Catania
country: Italy
facility: Divisione Ematologia - Oncologia Pediatrica Clinica Pediatrica
city: Catanzaro
country: Italy
facility: Unità Operativa di Ematologia ed Oncologia Pediatrica Az. Osp. "Pugliese-Ciaccio"
city: Cosenza
country: Italy
facility: Unità Operativa Pediatria Azienda Ospedaliera Annuziata
city: Ferrara
country: Italy
facility: Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria Università di Ferrara
city: Firenze
country: Italy
facility: Dipartimento A.I. Oncoematologia Pediatrica e Cure Domiciliari U.O. Oncoematologia Pediatrica Azienda Ospedaliero-Universitaria Meyer
city: Genova
country: Italy
facility: Dipartimento di Ematologia e Oncologia Pediatrica Instituto " G. Gaslini"
city: Lecce
country: Italy
facility: Ospedale "Vito Fazzi" U.O. di Pediatria
city: Milano
country: Italy
facility: Clinica Pediatrica II De Marchi
city: Milano
country: Italy
facility: Unità di Ricerca Clinica Pediatrica HSR TIGET - Istituto Scientifico San Raffaele
city: Milano
country: Italy
facility: Divisione di Oncologia Pediatrica Ist. Nazionale Studio e Cura Tumori
city: Milano
country: Italy
facility: Divisione Pediatria "Mariani" Ospedale "Niguarda Ca' Granda"
city: Modena
country: Italy
facility: U.O. di Ematologia, oncologia e trapianto Azienda Policlinico di Modena
city: Monza
country: Italy
facility: Clinica Pediatrica dell'Università Milano - Bicocca A.O. San Gerardo - Fondazione MBBM
city: Napoli
country: Italy
facility: Dipartimento di Oncologia A.O. Santobono - Pausilipon
city: Napoli
country: Italy
facility: A.O. "A. Cardarelli", U.O.S. Talassemia pediatrica ed emoglobinopatie pediatriche
city: Napoli
country: Italy
facility: Servizio di Oncologia Pediatrica Dipartimento di Pediatria Seconda Università degli Studi di Napoli
city: Nocera Inferiore
country: Italy
facility: U.O.C. Pediatria - TIN, Ospedale "Umberto Primo" ASL SA - 1
city: Novara
country: Italy
facility: S.C.D.U. Azienda Ospedaliera "Maggiore della carità"
city: Padova
country: Italy
facility: Dipartimento di Pediatria Università di Padova Cattedra Di Oncoematologia Pediatrica
city: Palermo
country: Italy
facility: Oncoematologia Pediatrica Ospedale dei Bambini G. di Cristina
city: Parma
country: Italy
facility: U.O. di Pediatria e Oncoematologia Pediatrica Az. Osp. Di Parma Ospedali Riuniti
city: Pavia
country: Italy
facility: Oncoematologia Pediatrica IRCCS, Policlinico San Matteo
city: Perugia
country: Italy
facility: S.C. di Oncoematologia Pediatrica con Trapianto di CSE, Ospedale "S.M. della Misericordia" A.O. Perugia
city: Pesaro
country: Italy
facility: Ematologia, Ospedale di Muraglia
city: Pesaro
country: Italy
facility: U.O. Pediatrica Azienda Ospedaliera San Salvatore
city: Pescara
country: Italy
facility: Dipartimento di Ematologia Ospedale Civile
city: Pisa
country: Italy
facility: Centro di Oncoematologia Pediatrica e Trapianto Midollo Osseo Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
city: Pordenone
country: Italy
facility: Centro Integrato di Emato-oncologia e dell'adolescenza A.O. S. Maria degli Angeli - Pordenone e IRCCS Centro di Riferimento Oncologico - Aviano
city: Reggio Calabria
country: Italy
facility: Divisione Ematologia Ospedali Riuniti
city: Rimini
country: Italy
facility: U.O Pediatria Ospedale Infermi Azienda USL Rimini
city: Roma
country: Italy
facility: Ospedale Sant'Eugenio clinica pediatrica Univ. Tor Vergata
city: Roma
country: Italy
facility: Oncoematologia pediatrica Università "La Sapienza" Roma
city: Roma
country: Italy
facility: Sezione Ematologia Dipart. di biotecnologie Cellulari ed Ematologia Università "La Sapienza"
city: Roma
country: Italy
facility: Divisione di Ematologia Pediatrica Ospedale "Bambin Gesù"Istituto di Ricerca Scientifica
city: Roma
country: Italy
facility: Divisione Oncologia Pediatrica Ospedale "Bambin Gesù"
city: Roma
country: Italy
facility: Divisione Oncologia Pediatrica Università Cattolica di Roma
city: San Giovanni Rotondo
country: Italy
facility: U.O. Oncoematologia Pediatrica Ospedale "Casa Sollievo della Sofferenza"
city: Sassari
country: Italy
facility: Clinica Pediatrica Università
city: Siena
country: Italy
facility: Dipartimento di Pediatria Ostetricia e Medicina della Riproduzione Università degli Studi di Siena
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita
city: Tricase
country: Italy
facility: Unità Operativa di Pediatria - U.T.I.N. Az.Osp. "Card. G. Panico"
city: Trieste
country: Italy
facility: U.O. Emato-Oncologia Pediatrica Università degli studi di Trieste Ospedale Infantile Burlo Garofolo
city: Udine
country: Italy
facility: SOS Oncologia Pediatrica Policlinico Universitario
city: Varese
country: Italy
facility: Clinica Pediatrica Università degli Studi dell'Insubria di Varese Ospedale "Filippo del Ponte"
city: Verona
country: Italy
facility: U.O.C Oncoematologia Pediatrica Policlinico "G.B: Rossi"
city: Vicenza
country: Italy
facility: Ospedale San Bortolo, U.O. di Pediatria e patologia Neonatale
city: Aarau
country: Switzerland
facility: Kinderklinik, Hämatologie/Onkologie
city: Basel
country: Switzerland
facility: Baseler Kinderspital, Hämatologische Poliklinik
city: Bellinzona
country: Switzerland
facility: Repartio di Pediatria
city: Luzern
country: Switzerland
facility: Pädiatrische Klinik, Kinderspital Luzern, Kinderonkologie
city: St. Gallen
country: Switzerland
facility: Hämatologie/Onkologie, Ostschweizer Kinderspital, FMH Pädiatrie, Hämatologie
city: Zürich
country: Switzerland
facility: Kinderspital Zürich, Universitäts-Kinderklinik
Study officials:
affiliation: Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel
name: Martin Schrappe, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A, Arico M, Zimmermann M, Mann G, De Rossi G, Stanulla M, Locatelli F, Basso G, Niggli F, Barisone E, Henze G, Ludwig WD, Haas OA, Cazzaniga G, Koehler R, Silvestri D, Bradtke J, Parasole R, Beier R, van Dongen JJ, Biondi A, Schrappe M. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010 Apr 22;115(16):3206-14. doi: 10.1182/blood-2009-10-248146. Epub 2010 Feb 12.
citation: Flohr T, Schrauder A, Cazzaniga G, Panzer-Grumayer R, van der Velden V, Fischer S, Stanulla M, Basso G, Niggli FK, Schafer BW, Sutton R, Koehler R, Zimmermann M, Valsecchi MG, Gadner H, Masera G, Schrappe M, van Dongen JJ, Biondi A, Bartram CR; International BFM Study Group (I-BFM-SG). Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia. 2008 Apr;22(4):771-82. doi: 10.1038/leu.2008.5. Epub 2008 Jan 31.
citation: Moricke 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.
citation: Wurthwein G, Lanvers-Kaminsky C, Siebel C, Gerss J, Moricke 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.
citation: 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. No abstract available.
citation: 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.
citation: 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.
citation: Wurthwein G, Lanvers-Kaminsky C, Hempel G, Gastine S, Moricke A, Schrappe M, Karlsson MO, Boos J. Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar(R) in Children with Acute Lymphoblastic Leukemia. Eur J Drug Metab Pharmacokinet. 2017 Dec;42(6):955-963. doi: 10.1007/s13318-017-0410-5.