Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
The understanding of acute lymphoblastic leukemia (ALL) in childhood and adolescence has largely changed due to extensive genetic research in recent years: ALL is now considered to be a very heterogeneous disease group. The leukemia cells present themselves with quite differently activated regulatory mechanisms of the malignant phenotype. The introduction of more accurate methods of assessing therapy response ("minimal residual disease [MRD] tests") has provided new insights into very different mechanisms of action, including factors influenced by host factors; this has had practical clinical consequences for the use of more individualized therapy. Multimodal therapies have enabled a cure level of over 80% for ALL in this age group. However, the own and international study data show that the therapy toxicity of the contemporary chemotherapy concepts has become unacceptably high, in particular with respect to those intensified therapies used for the treatment of patients at high risk of ALL relapse.
The AIEOP-BFM ALL 2017 study therefore aims for an innovative integrated approach that will not only adapt the risk stratification to new prognostic markers using more comprehensive diagnostics, but above all, qualitatively reorient the therapy. The most important consequence will be that this study is testing immunotherapy with the bispecific antibody blinatumomab as an alternative to particularly intensive and toxic chemotherapy elements in precursor B-cell ALL (pB-ALL) patients with detectable chemotherapy resistance and at high risk of relapse. With the aim to complement the effects of the conventional chemotherapy, Blinatumomab is in addition tested in the large group of pB-ALL patients at intermediate relapse risk with seemingly unremarkable leukemia, but who account for a large proportion of all relapses. Targeted therapy is also used in the form of the proteasome inhibitor bortezomib for patients with pB-ALL and slow response to the drugs of the induction chemotherapy with the aim to overcome intrinsic chemotherapy resistance of the ALL cells. In patients with T-lineage ALL, who have particularly poor chances for cure after relapse, the established consolidation chemotherapy has proved to be particularly effective. This chemotherapy phase is therefore tested in a longer and more intensive form in such T-ALL patients with intermediate or slow early treatment response with the aim to reduce the relapses rate in this subgroup.
Study Overview
Status
Conditions
Intervention / Treatment
- Drug: Cyclophosphamide
- Drug: Cytarabine
- Drug: Daunorubicin
- Drug: Dexamethasone
- Drug: Doxorubicin
- Drug: 6-Mercaptopurine
- Drug: Methotrexate
- Drug: Pegaspargase
- Drug: Prednisolone
- Drug: Tioguanin
- Drug: Vincristine
- Drug: Erwinase
- Drug: Bortezomib
- Drug: Blinatumomab
- Drug: Myocet
- Drug: Etoposide
- Drug: Fludarabine Phosphate
- Drug: Ifosfamide
- Drug: Vindesine
Detailed Description
Patients are stratified into 4 early risk groups for therapy during the consolidation phase (T/early SR, T/early non-SR, pB/early non-HR, pB/early HR) and 5 risk groups for post-consolidation therapy (T/non-HR, T/HR, pB/SR, pB/MR, pB/HR). Risk stratification is based on immunophenotypic lineage, genetics of leukemic cells and treatment response on the basis of cytomorphology and methods for detection minimal residual disease.
The trial includes four randomized study questions testing experimental treatments on top of the risk-stratified standard chemotherapy backbone:
Primary study questions:
Randomization R-eHR: Early High-risk (early HR) pB-ALL defined by genetics and/or inadequate treatment response over the course of induction: Can the probability of event-free survival (pEFS) from time of randomization be improved by additional therapy with the proteasome inhibitor bortezomib during an extended consolidation treatment phase compared with standard extended consolidation?
Randomization R-HR: High-risk (HR) pB-ALL defined by genetics and/or inadequate treatment response by the end of consolidation: Can the pEFS from time of randomization be improved by a treatment concept including two cycles of post-consolidation immunotherapy with blinatumomab (15 µg/m²/d for 28 days per cycle) plus 4 doses intrathecal Methotrexate replacing two conventional highly intensive chemotherapy courses?
Randomization R-MR: Intermediate risk (MR) pB-ALL defined by genetics and intermediate MRD response: Can the probability of disease-free survival (pDFS) from time of randomization be improved by additional therapy with one cycle of post-reintensification immunotherapy with blinatumomab (15 µg/m²/d for 28 days)?
Randomization R-T: Early non-standard risk (early non-SR) T-ALL patients defined by treatment response over the course of induction: Can the pEFS from time of randomization be improved by the extension of the standard of care consolidation phase by 14 days with an increase of the consolidation cumulative doses of Cyclophosphamide, Cytarabine and 6-Mercaptopurine by 50%?
Secondary study questions:
All randomizations: Can the overall survival be improved by the treatment in the experimental arm?
All randomizations: What is the incidence of treatment-related toxicities and mortality in the experimental arm compared to the standard arm?
Randomization R-eHR: Can the MRD load after consolidation treatment be reduced by the additional treatment with bortezomib?
Randomization R-HR: Can treatment-related life-threatening complications and mortality during the intensified consolidation phase of high-risk treatment be reduced when replacing two intensive chemotherapy courses by two cycles of immunotherapy with blinatumomab?
Randomization R-HR: What is the proportion of patients with insufficient MRD response to blinatumomab as defined in the protocol as compared to the MRD response after the HR-2' block in the control arm?
Randomization R-HR: Can the MRD load after the first treatment cycle (HR 2'/blinatumomab) and the second cycle (HR-3'/blinatumomab) be reduced in the experimental arm when compared with conventional intensive chemotherapy? Randomization R-MR: What is the proportion of patients with positive MRD after reintensification Protocol II who become MRD-negative over the blinatumomab cycle compared to 4 weeks of standard maintenance therapy?
Randomization R-T: Can the MRD load after consolidation treatment be reduced by extension of the consolidation phase?
Standard-risk patients: Is the clinical outcome comparable to that obtained for standard-risk patients in study AIEOP-BFM ALL 2009?
A small subgroup of patients at very high relapse risk is eligible for allogeneic hematopoietic stem cell transplantation after the intensified consolidation therapy phase.
Patients with T-ALL and hyperleukocytosis (>=100,000/µL) and patients with CNS involvement at diagnosis (CNS3 status) are eligible for cranial irradiation with 12 Gy if age at time of irradiation is at least 4 years.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Anja Möricke, MD
- Phone Number: +4943150020150
- Email: a.moericke@pediatrics.uni-kiel.de
Study Contact Backup
- Name: Lile Bauer
- Phone Number: +4943150020152
- Email: lile.bauer@uksh.de
Study Locations
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Sydney, Australia
- Recruiting
- Sydney Children's Hospital
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Contact:
- Draga Barbaric
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Westmead, Australia
- Recruiting
- The Children's Hospital at Westmead
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Contact:
- Luciano Dalla-Pozza
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Graz, Austria
- Recruiting
- Univ.Klinik für Kinder- und Jugendheilkunde Graz
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Contact:
- Martin Benesch
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Innsbruck, Austria
- Recruiting
- Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck
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Contact:
- Bernhard Meister
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Linz, Austria
- Recruiting
- Kepler Universitätsklinikum
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Contact:
- Georg Ebetsberger
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Salzburg, Austria
- Recruiting
- LKH Salzburg
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Contact:
- Neil Jones
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Vienna, Austria
- Recruiting
- St. Anna Kinderspital
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Contact:
- Andishe Attarbaschi
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Brno, Czechia
- Recruiting
- University Hospital Brno
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Contact:
- Jaroslav Štěrba
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Hradec Králové, Czechia
- Recruiting
- University Hospital Hradec Kralove
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Contact:
- Jiří Hak
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Olomouc, Czechia
- Recruiting
- University Hospital Olomouc
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Contact:
- Dagmar Pospíšilová
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Ostrava-Poruba, Czechia
- Recruiting
- University Hospital Ostrava-Poruba
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Contact:
- Tomáš Kuhn
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Plzeň, Czechia
- Recruiting
- University Hospital Plzen
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Contact:
- Tomáš Votava
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Praha, Czechia
- Recruiting
- University Hospital Motol
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Contact:
- Jan Starý
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Ústí nad Labem, Czechia
- Recruiting
- Masaryk´s Hospital Ústí nad Labem
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Contact:
- Daniela Procházková
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České Budějovice, Czechia
- Recruiting
- Regional Hospital Ceské Budejovice
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Contact:
- Pavel Timr
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Aachen, Germany, 52074
- Recruiting
- Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
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Contact:
- Udo Kontny
- Phone Number: 9902 +49 241808
- Email: ukontny@ukaachen.de
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Augsburg, Germany, 86156
- Recruiting
- I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
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Contact:
- Michael Frühwald
- Phone Number: 3631 +49 821400
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Berlin, Germany, 13125
- Recruiting
- Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
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Contact:
- Lothar Schweigerer
- Phone Number: 2367 +49 309401
- Email: lschweigerer@berlin.helio-kliniken.de
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Berlin, Germany, 13353
- Recruiting
- Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
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Contact:
- Arend Stackelberg
- Phone Number: 833 +49 30450566
- Email: arend.stackelberg@charite.de
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Braunschweig, Germany, 38118
- Recruiting
- Städtisches Krankenhaus, Kinderklinik
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Contact:
- Wolfgang Eberl
- Phone Number: 1424 +49 531595
- Email: w.eberl@klinkum-braunschweig.de
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Chemnitz, Germany, 09009
- Recruiting
- Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
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Contact:
- Andre Hofmann
- Phone Number: 4287 +49 3713332
- Email: a.hofmann@skc.de
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Cottbus, Germany, 03048
- Recruiting
- Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
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Contact:
- Georg Schwabe
- Phone Number: 2332 +49 35546
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Datteln, Germany, 45711
- Recruiting
- Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
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Contact:
- Thomas Wiesel
- Phone Number: 5846 +49 236397
- Email: th.wiesel@kinderklinik-datteln.de
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Dortmund, Germany, 44137
- Recruiting
- Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
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Contact:
- Dominik Schneider
- Phone Number: 1050 +49 2319532
- Email: dominik.schneider@klinikumdo.de
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Dresden, Germany, D-01307
- Recruiting
- Universitätsklinikum Carl Gustav Carus
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Contact:
- R. Knöfler, MD
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Düsseldorf, Germany
- Recruiting
- Universitätsklinik
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Contact:
- Arndt Borkhardt, Prof.
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Erfurt, Germany, 99089
- Recruiting
- Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
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Contact:
- Axel Sauerbrey
- Phone Number: 4501 +49 36178
- Email: axel.sauerbrey@helios-kliniken.de
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Erlangen, Germany, 91054
- Recruiting
- Universitaets - Kinderklinik
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Contact:
- M. Metzler, MD
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Essen, Germany, D-45147
- Recruiting
- Universitaetsklinikum Essen
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Contact:
- Rita Beier, MD
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Frankfurt, Germany, D-60590
- Recruiting
- Klinikum der J.W. Goethe Universitaet
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Contact:
- Thomas Klingebiel, MD
- Phone Number: 49-69-6301-5094
- Email: thomas.klingebiel@kgu.de
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Freiburg, Germany, D-79106
- Recruiting
- Universitaetskinderklinik - Universitaetsklinikum Freiburg
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Contact:
- Charlotte Niemeyer, MD
- Phone Number: 49-761-270-4506
- Email: charlotte.niemeyer@uniklinik-freiburg.de
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Gießen, Germany, 35385
- Recruiting
- Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
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Contact:
- Christine Mauz-Körholz
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Greifswald, Germany, 17475
- Recruiting
- Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
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Contact:
- Holger Lode
- Phone Number: 6325 +49 383486
- Email: holger.lode@uni-greifswald.de
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Göttingen, Germany, 37099
- Recruiting
- Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
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Contact:
- Ingrid Kühnle
- Phone Number: 6201 +49 55139
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Hannover, Germany, 30625
- Recruiting
- Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
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Contact:
- Christin Linderkamp
- Phone Number: 6710 +49 511532
- Email: linderkamp.christin@mh-hannover.de
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Heidelberg, Germany, 69120
- Recruiting
- Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
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Contact:
- Wolfgang Behnisch
- Phone Number: 4555 +49 622156
- Email: wolfgang.behnisch@med.uni-heidelberg.de
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Heilbronn, Germany, 74078
- Recruiting
- Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
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Contact:
- Hermann Full
- Phone Number: 3702 +49 713149
- Email: hermann.full@slk-kliniken.de
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Herdecke, Germany, 58313
- Recruiting
- Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
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Contact:
- Alfred Längler
- Phone Number: 3893 +49 233062
- Email: a.laengler@gemeinschaftskrankenhaus.de
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Homburg, Germany, 66421
- Recruiting
- Universitaetsklinikum Des Saarlandes
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Contact:
- Norbert Graf
- Phone Number: 49-6841-168-8397
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Jena, Germany, 7740
- Recruiting
- Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
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Contact:
- Bernd Gruhn
- Phone Number: 8220 +49 364193
- Email: bernd.gruhn@med.uni-jena.de
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Karlsruhe, Germany, 76133
- Recruiting
- Staedtisches Klinikum Karlsruhe gGmbH
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Contact:
- A. Leipold
- Phone Number: 49-721-9740
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Kassel, Germany, D-34125
- Recruiting
- Klinikum Kassel
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Contact:
- Michaela Nathrath, MD
- Phone Number: 49-561-980-3382
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Kiel, Germany, 24105
- Recruiting
- Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
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Contact:
- Martin Schrappe
- Phone Number: 1620 +49 431597
- Email: m.schrappe@pediatrics.uni-kiel.de
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Köln, Germany, 50735
- Recruiting
- Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
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Contact:
- Aram Prokop
- Phone Number: 5158 +49 2218907
- Email: prokopa@klinken-koeln.de
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Köln, Germany, 50937
- Recruiting
- Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
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Contact:
- Thorsten Simon
- Phone Number: 4380 +49 221478
- Email: thorsten.simon@uk-koeln.de
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Leipzig, Germany, 04103
- Recruiting
- Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
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Contact:
- Lars Fischer
- Phone Number: 0341-97 26
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Lübeck, Germany, 23538
- Recruiting
- Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
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Contact:
- Melchior Lauten
- Phone Number: 2557 +49 451500
- Email: lauten@paedia.ukl.mu-luebeck.de
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Magdeburg, Germany, 39120
- Recruiting
- Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
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Contact:
- Peter Vorwerk
- Phone Number: 7210 +49 391671
- Email: peter.vorwerk@med.ovgu.de
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Mannheim, Germany, 68167
- Recruiting
- Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
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Contact:
- Matthias Dürken
- Phone Number: 2244 +49 621383
- Email: matthias.duerken@kikli.ma.uni-heidelberg.de
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Mannheim, Germany
- Recruiting
- Universitätsklinikum
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Contact:
- Matthias Dürken, Dr.
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Minden, Germany, 32429
- Recruiting
- Johannes Wesling Klinikum Minden
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Contact:
- Bernhard Erdlenbruch
- Phone Number: 8010 +49 571
- Email: bernhard.erdlenbruch@klinikum-minden.de
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München, Germany, 80804
- Recruiting
- Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
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Contact:
- Angela Wawer
- Phone Number: 2261 +49 893068
- Email: angela.wawer@lrz.tum.de
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München, Germany
- Recruiting
- Ludwig-Maximilian-Universität, Dr. von Haunersches Kinderspital
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Contact:
- Tobias Feuchtinger
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Münster, Germany, 48149
- Recruiting
- Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
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Contact:
- Claudia Rössig
- Phone Number: 5644 +49 251834
- Email: rossig@ukmuenster.de
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Nürnberg, Germany, 90419
- Recruiting
- Cnopf'sche Kinderklinik, Onkologie
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Contact:
- Wolfram Scheurlen
- Phone Number: 40323 +49 91133
- Email: wolfram.scheurlen@diakonieneudettelsau.de
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Oldenburg, Germany, 26133
- Recruiting
- Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
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Contact:
- Hermann Müller
- Phone Number: 2013 +49 441403
- Email: mueller.hermann@klinikum-oldenburg.de
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Regensburg, Germany
- Recruiting
- Universitätsklinikum
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Contact:
- Selim Corbacioglu, Dr.
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Rostock, Germany, 18055
- Recruiting
- Universitäts-Kinderklinik
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Contact:
- Carl-Friedrich Classen
- Phone Number: 7000 +49 381494
- Email: carl-friedrich.classen@med.uni-rostock.de
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Sankt Augustin, Germany, 53757
- Recruiting
- Asklepios-Klinik, Sankt Augustin GmbH
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Contact:
- Harald Reinhard
- Phone Number: 9304 +49 224124
- Email: h.reinhard@asklepios.com
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Schwerin, Germany, 19049
- Recruiting
- HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
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Contact:
- Christian Güttel
- Phone Number: 2710 +49 385520
- Email: christian.guettel@helios-kliniken.de
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Stuttgart, Germany, 70176
- Recruiting
- Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
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Contact:
- Stefan Bielack
- Phone Number: 2461 +49 711992
- Email: st.bielack@olgahospital.de
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Trier, Germany, 54290
- Recruiting
- Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
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Contact:
- Stefan Weis
- Phone Number: 2654 +49 651947
- Email: weis@mutterhaus.de
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Tuebingen, Germany, D-72076
- Recruiting
- Universitaetsklinikum Tuebingen
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Contact:
- Martin Ebinger, MD
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Ulm, Germany, D-89075
- Recruiting
- Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
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Contact:
- Klaus M. Debatin, MD
- Phone Number: 49-731-5000
- Email: klaus-michael.debatin@medizin.uni-ulm.de
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Wolfsburg, Germany, 38440
- Recruiting
- Stadtkrankenhaus, Kinderklinik
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Contact:
- Sally Mukodzi
- Phone Number: 8000 +49 5361
- Email: sally.mukidzi@klinikum-wolfsburg.de
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Wuerzburg, Germany, D-97080
- Recruiting
- Universitaets - Kinderklinik Wuerzburg
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Contact:
- P. G. Schlegel, MD
- Phone Number: 49-931-2012-7856
- Email: schlegel@mail.uni-wuerzburg.de
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Beer Sheva, Israel
- Recruiting
- Soroka University Medical Center
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Contact:
- Joseph Kapelushnik
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Haifa, Israel
- Recruiting
- Rambam Health Care Campus
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Contact:
- Nira Arad-Cohen
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Jerusalem, Israel
- Recruiting
- Hadassah Medical Center
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Contact:
- Gal Goldstein
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Petach-Tikva, Israel
- Recruiting
- Schneider Children Medical Center of Israel
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Contact:
- Gil Gilad
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Ramat Gan, Israel
- Recruiting
- Sheba Medical Center Tel-Hashomer
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Contact:
- Bella Bielorai
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Tel-Aviv, Israel
- Recruiting
- Dana children hospital
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Contact:
- Ronit Elhasid
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Ancona, Italy
- Recruiting
- Azienda ospedali riuniti
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Contact:
- Paolo Pierani
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Bari, Italy
- Recruiting
- AOUC Policlinico Bari
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Contact:
- Nicola Santoro
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Bergamo, Italy
- Recruiting
- A.O. Papa Giovanni XXIII
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Contact:
- Massimo Provenzi
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Bologna, Italy
- Recruiting
- Universita di Bologna
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Contact:
- Andrea Pession
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Brescia, Italy
- Recruiting
- Asst Spedali Civili Di Brescia
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Contact:
- Fulvio Porta
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Cagliari, Italy
- Recruiting
- Ospedale Businco
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Contact:
- Rosa Maria Mura
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Catania, Italy
- Recruiting
- Azienda Ospedaliero Universitaria
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Contact:
- Luca Lo Nigro
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Catanzaro, Italy
- Recruiting
- AO Pugliese Ciaccio
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Contact:
- Caterina Consarino
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Cosenza, Italy
- Recruiting
- S.O. Annunziata - A. O. Cosenza
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Contact:
- Domenico Sperlì
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Firenze, Italy
- Recruiting
- Ospedale Meyer
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Contact:
- Tommaso Casini
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Genova, Italy
- Recruiting
- Istituto Giannina Gaslini
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Contact:
- Concetta Micalizzi
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Modena, Italy
- Recruiting
- Policlinico di Modena Azienda Ospedaliero-Universitaria
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Contact:
- Monica Cellini
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Monza, Italy
- Recruiting
- Clinica pediatrica Fondazione MBBM
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Contact:
- Andrea Biondi
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Napoli, Italy
- Recruiting
- A.O.U. Vanvitelli
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Contact:
- Francesca Rossi
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Napoli, Italy
- Recruiting
- Aorn Santobono Pausilipon
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Contact:
- Rosanna Parasole
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Padova, Italy
- Recruiting
- Azienda Ospedaliera Di Padova
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Contact:
- Maria Caterina Putti
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Palermo, Italy
- Recruiting
- Ospedale Civico ARNAS Civico e Di Cristina
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Contact:
- Ottavio Ziino
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Parma, Italy
- Recruiting
- Azienda Ospedaliero-Universitaria di Parma
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Contact:
- Angelica Barone
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Pavia, Italy
- Recruiting
- Fondazione IRCCS Policlinico San Matteo
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Contact:
- Marco Zecca
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Perugia, Italy
- Recruiting
- Ospedale S. Maria Della Misericordia
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Contact:
- Maurizio Caniglia
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Pescara, Italy
- Recruiting
- Ospedale Civile di Pescara
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Contact:
- Daniela Onofrillo
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Pisa, Italy
- Recruiting
- Ospedale Santa Chiara Pisa
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Contact:
- Emanuela De Marco
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Reggio Calabria, Italy
- Recruiting
- Grande ospedale metropolitano B-M-M
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Contact:
- Francesca Ronco
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Rimini, Italy
- Recruiting
- Ospedale Infermi
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Contact:
- Roberta Pericoli
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Roma, Italy
- Recruiting
- Ospedale Bambino Gesu
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Contact:
- Franco Locatelli
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Roma, Italy
- Recruiting
- Fondazione Policlinico Gemelli
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Contact:
- Antonio Ruggiero
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Roma, Italy
- Recruiting
- Policlinico Umberto I Università Sapienza di Roma
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Contact:
- Robin Foà
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San Giovanni Rotondo, Italy
- Recruiting
- Ospedale "Casa sollievo della sofferenza"
-
Contact:
- Saverio Ladogana
-
Torino, Italy
- Recruiting
- A.O.U. Città della Salute e della Scienza di Torino
-
Contact:
- Franca Fagioli
-
Trieste, Italy
- Recruiting
- IRCCS Burlo Garofolo
-
Contact:
- Valentina Kiren
-
Verona, Italy
- Recruiting
- AOU Verona
-
Contact:
- Simone Cesaro
-
-
-
-
-
Banská Bystrica, Slovakia
- Recruiting
- Klinika pediatrickej hematológie a onkológie SZU a DFNsP
-
Contact:
- Eva Bubanská
-
Bratislava, Slovakia
- Recruiting
- Comenius University Children's Hospital
-
Contact:
- Alexandra Kolenova
-
Košice, Slovakia
- Recruiting
- Detska Fakultna nemocnica Kosice
-
Contact:
- Natália Galóová
-
-
-
-
-
Aarau, Switzerland
- Recruiting
- Kantonsspital Aarau
-
Contact:
- Katrin Scheinemann
-
Basel, Switzerland
- Recruiting
- Universitäts-Kinderspital beider Basel
-
Contact:
- Nicolas von der Weid
-
Bellinzona, Switzerland
- Recruiting
- Ospedale San Giovanni Bellinzona
-
Contact:
- Pierluigi Brazzola
-
Bern, Switzerland
- Recruiting
- Inselspital Bern
-
Contact:
- Jochen Rössler
-
Genève, Switzerland
- Recruiting
- HUG Hôpitaux Universitaires de Gèneve
-
Contact:
- Frederic Baleydier
-
Lausanne, Switzerland
- Recruiting
- CHUV centre hospitalier universitaire vaudois
-
Contact:
- Francesco Ceppi
-
Luzern, Switzerland
- Recruiting
- Luzerner Kantonsspital-Kinderspital Luzern
-
Contact:
- Freimut Schilling
-
St. Gallen, Switzerland
- Recruiting
- Ostschweizer Kinderspital
-
Contact:
- Jeanette Greiner
-
Zürich, Switzerland
- Recruiting
- Universitäts-Kinderspital Zürich
-
Contact:
- Felix Niggli
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- newly diagnosed acute lymphoblastic leukemia or
- newly diagnosed mixed phenotype acute leukemia (MPAL) meeting one of the following criteria:
- biphenotypic with a dominant T or B lineage assignment
- bilineal either with a dominant lymphoblastic population or if another reasonable rationale exists to treat the patient with an ALL-based therapy regimen
- newly diagnosed acute undifferentiated leukemia
- age < 18 years (up to 17 years and 365 days) at the day of diagnosis
- patient enrolled in a participating center
- written informed consent to trial participation and transfer and processing of data A subsequent removal from the study is only allowed if the inclusion criteria turn out not to be fulfilled or in the case of pregnancy of the patient.
Exclusion Criteria:
- Ph+ (BCR-ABL1 or t(9;22)-positive) ALL
- bilineal leukemia with a lymphoblastic and a separate non-lymphoblastic (≥ 10% of total cells) blast subset
- pre-treatment with cytostatic drugs
- glucocorticoid 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 disease that does not allow treatment according to the protocol (e.g. severe congenital heart disease, Charcot-Marie Syndrome, Ataxia-teleangiectasia…)
- ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
- evidence of pregnancy or lactation period
- Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of anti-leukemic therapy
- participation in another clinical trial except for add-on trials within the scope of supportive care approved by the sponsor
- live vaccine immunization within 2 weeks before start of protocol treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX) Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)] Erwinase is given in case of allergy to pegaspargase. |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
|
|
Experimental: pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59) Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)] Erwinase is given in case of allergy to pegaspargase. |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Experimental therapy in randomization R-eHR
|
|
Experimental: pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR) Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Experimental therapy in randomizations R-HR and R-MR
|
|
Experimental: pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59) Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR) Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Experimental therapy in randomization R-eHR
Experimental therapy in randomizations R-HR and R-MR
|
|
Active Comparator: pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX). |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
|
|
Experimental: pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59) Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX) |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
|
|
Experimental: pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR) Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX) |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Experimental therapy in randomizations R-HR and R-MR
Part of intensification block Myocet-FLA for patients with very high relapse risk
|
|
Experimental: pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59) Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR) Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX) |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Experimental therapy in randomizations R-HR and R-MR
Part of intensification block Myocet-FLA for patients with very high relapse risk
|
|
Other: pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
|
|
Active Comparator: T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR" HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX) |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
|
|
Experimental: T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR" HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX) |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
|
|
Other: T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX Erwinase is given in case of allergy to pegaspargase. |
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T and in the intensification block Myocet-FLA for patients with very high relapse risk
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy
Other Names:
Part of standard chemotherapy
Part of standard chemotherapy
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Event-free survival
Time Frame: Assessed up to 120 months from start of study
|
Randomization R-eHR, R-HR and R-T: Time from randomization until the first event defined as follow: cytomorphological or molecular non-response (resistance to protocol treatment, considered as event at day zero), relapse, second malignancy or death from any cause.
This will be called EFS time.
|
Assessed up to 120 months from start of study
|
|
Disease-free survival
Time Frame: Assessed up to 120 months from start of study
|
Randomization R-MR: Time from randomization until the first event defined as follow: Relapse, second malignancy or death from any cause.
This will be called DFS time.
|
Assessed up to 120 months from start of study
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Survival
Time Frame: Assessed up to 120 months from start of study
|
All patients/randomizations: Time until death from any cause, starting at the same time point as the EFS/DFS.
|
Assessed up to 120 months from start of study
|
|
Treatment-related mortality
Time Frame: Assessed up to 120 months from start of study
|
Frequency and incidence of treatment-related mortality in induction or continuous complete remission
|
Assessed up to 120 months from start of study
|
|
Adverse Events of interest/Serious Adverse Events
Time Frame: Assessed up to 120 months from start of study
|
Frequency and incidence of adverse events of interest and serious adverse events in specific protocol phases, randomized arms and overall during follow-up
|
Assessed up to 120 months from start of study
|
|
MRD response
Time Frame: Measurements of MRD response at end of randomized treatments (intended time frame 13 weeks in R-eHR/R-T, 26 weeks in R-HR, 34 weeks in R-MR).
|
MRD load after the randomized treatment phases (R-eHR, R-HR, R-MR and R-T) as well as after the first/second cycle of Blinatumomab or after the HR 2'/HR 3' block (R-HR)
|
Measurements of MRD response at end of randomized treatments (intended time frame 13 weeks in R-eHR/R-T, 26 weeks in R-HR, 34 weeks in R-MR).
|
|
Proportion of patients with Blina Poor-Response
Time Frame: Measurements of MRD response intended after 30 weeks from individual start of treatment, assessment of proportion at 120 months from start of study
|
Proportion of patients with poor MRD response to the first Blinatumomab cycle ("Blinatumomab Poor-Response") (R-HR)
|
Measurements of MRD response intended after 30 weeks from individual start of treatment, assessment of proportion at 120 months from start of study
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Martin Schrappe, MD, Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Antibiotics, Antineoplastic
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Dexamethasone
- Prednisolone
- Cyclophosphamide
- Etoposide
- Ifosfamide
- Prednisone
- Bortezomib
- Doxorubicin
- Fludarabine
- Fludarabine phosphate
- Cytarabine
- Methotrexate
- Vincristine
- Daunorubicin
- Asparaginase
- Mercaptopurine
- Blinatumomab
- Pegaspargase
- Vindesine
Other Study ID Numbers
- AIEOP-BFM ALL 2017
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Lymphoblastic Leukemia, Pediatric
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Emory UniversityTerminatedPediatric Acute Myeloblastic Leukemia, Relapsed | Pediatric Acute Lymphoblastic Leukemia, RelapsedUnited States
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Indiana UniversityNational Institute of Nursing Research (NINR); Ann & Robert H Lurie Children... and other collaboratorsRecruitingAcute Lymphoblastic Leukemia, Pediatric | Pediatric CancerUnited States
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Tanja Andrea GruberRecruitingAcute Lymphoblastic Leukemia, Pediatric | Refractory Acute Lymphoblastic Leukemia | Relapsed Acute Lymphoblastic LeukemiaUnited States
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MedImmune LLCTerminatedB-Cell Pediatric ALLUnited States, Australia, France, Spain, Canada, Netherlands, United Kingdom, Italy
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University of BirminghamAstraZeneca; Cancer Research UKTerminatedAcute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia, Adult | Acute Lymphoblastic Leukemia RecurrentUnited Kingdom, Denmark, Netherlands
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Beijing Boren HospitalRecruitingAcute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Refractory Acute Lymphoblastic LeukemiaChina
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University College, LondonNot yet recruitingAcute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia, Adult | Acute Lymphoblastic Leukemia With Failed Remission | Acute Lymphoblastic Leukemia Not Having Achieved Remission
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Medical College of WisconsinChildren's Hospital and Health System Foundation, WisconsinRecruitingAcute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia, Pediatric | Acute Lymphoblastic Leukemia, in Relapse | Acute Lymphoblastic Leukemia Recurrent | Acute Lymphoblastic Leukemia With Failed Remission | Acute Lymphoblastic Leukemia Not Having Achieved RemissionUnited States
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Children's Mercy Hospital Kansas CityCompletedRefractory Acute Myeloid Leukemia | Refractory Acute Lymphoblastic Leukemia | Relapsed Pediatric AML | Relapsed Pediatric ALLUnited States
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Columbia UniversityAmerican Cancer Society, Inc.; Gabrielle's Angel FoundationActive, not recruitingAcute Lymphoblastic Leukemia, Pediatric | Obesity, PediatricUnited States
Clinical Trials on Cyclophosphamide
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Children's Hospital Los AngelesLucile Packard Children's HospitalTerminatedMetabolic Diseases | Stem Cell Transplantation | Chronic Granulomatous Disease | Bone Marrow Transplantation | Thalassemia | Wiskott-Aldrich Syndrome | Genetic Diseases | Peripheral Blood Stem Cell Transplantation | Pediatrics | Diamond-Blackfan Anemia | Allogeneic Transplantation | Combined Immune Deficiency | X-linked Lymphoproliferative Disease
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Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedAnemia, AplasticUnited States
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Columbia UniversityUnknownSevere Combined Immunodeficiency | Fanconi Anemia | Bone Marrow Failure | OsteopetrosisUnited States
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National Cancer Institute, NaplesImmatics Biotechnologies GmbH; CureVac; European Commission -FP7-Health-2013-Innovation-1CompletedHepatocellular CarcinomaBelgium, Germany, Italy, Spain, United Kingdom
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Mahidol UniversityTerminatedRenal Insufficiency | InfectionThailand
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Eisai Inc.CompletedBreast Cancer | Ovarian Cancer | Prostate Cancer | Colon Cancer | Renal CancerUnited States
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Centre Oscar LambretCompleted
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Baylor Research InstituteCompletedMalignant Melanoma Stage IVUnited States
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University of Turin, ItalyUnknown
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Merck KGaA, Darmstadt, GermanyCompleted