Acute Lymphoblastic Leukemia, PediatricPhase 3NCT03643276

Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017

A Phase 3 study testing Blinatumomab, Bortezomib and Cyclophosphamide in people with Acute Lymphoblastic Leukemia, Pediatric, run by Martin Schrappe at 115 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages Up to 17 years
Conditions the study is for: Acute Lymphoblastic Leukemia, Pediatric
What is being tested?: Blinatumomab, Bortezomib and Cyclophosphamide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5,000 participants
Where: 115 sitesin 8 countries
Study dates: 15 Jul 2018to 14 Jul 2028
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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…)

Show all 11Show fewer

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

Trial locations and contacts

115 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

Anja Möricke, MD contact

+4943150020150

a.moericke@pediatrics.uni-kiel.de

Lile Bauer contact

+4943150020152

lile.bauer@uksh.de

Country

City, postcode or hospital

Sites recruiting now only

115 sites in 8 countries

Germany51 sites, 51 recruiting

Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
Aachen, 52074
Udo Kontny, +49 241808 ext. 9902, ukontny@ukaachen.de
Recruiting
I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
Augsburg, 86156
Michael Frühwald, +49 821400 ext. 3631
Recruiting
Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
Berlin, 13125
Lothar Schweigerer, +49 309401 ext. 2367, lschweigerer@berlin.helio-kliniken.de
Recruiting
Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
Berlin, 13353
Arend Stackelberg, +49 30450566 ext. 833, arend.stackelberg@charite.de
Recruiting
Städtisches Krankenhaus, Kinderklinik
Braunschweig, 38118
Wolfgang Eberl, +49 531595 ext. 1424, w.eberl@klinkum-braunschweig.de
Recruiting
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
Chemnitz, 09009
Andre Hofmann, +49 3713332 ext. 4287, a.hofmann@skc.de
Recruiting
Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
Cologne, 50735
Aram Prokop, +49 2218907 ext. 5158, prokopa@klinken-koeln.de
Recruiting
Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
Cologne, 50937
Thorsten Simon, +49 221478 ext. 4380, thorsten.simon@uk-koeln.de
Recruiting
Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
Cottbus, 03048
Georg Schwabe, +49 35546 ext. 2332
Recruiting
Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
Datteln, 45711
Thomas Wiesel, +49 236397 ext. 5846, th.wiesel@kinderklinik-datteln.de
Recruiting
Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
Dortmund, 44137
Dominik Schneider, +49 2319532 ext. 1050, dominik.schneider@klinikumdo.de
Recruiting
Universitatsklinikum Carl Gustav Carus
Dresden, D-01307
R. Knöfler, MD
Recruiting
Universitätsklinik
Düsseldorf
Arndt Borkhardt, Prof.
Recruiting
Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
Erfurt, 99089
Axel Sauerbrey, +49 36178 ext. 4501, axel.sauerbrey@helios-kliniken.de
Recruiting
Universitaets - Kinderklinik
Erlangen, 91054
M. Metzler, MD
Recruiting
Universitaetsklinikum Essen
Essen, D-45147
Rita Beier, MD
Recruiting
Klinikum der J.W. Goethe Universitaet
Frankfurt, D-60590
Thomas Klingebiel, MD, 49-69-6301-5094, thomas.klingebiel@kgu.de
Recruiting
Universitaetskinderklinik - Universitaetsklinikum Freiburg
Freiburg im Breisgau, D-79106
Charlotte Niemeyer, MD, 49-761-270-4506, charlotte.niemeyer@uniklinik-freiburg.de
Recruiting
Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
Giessen, 35385
Christine Mauz-Körholz
Recruiting
Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
Göttingen, 37099
Ingrid Kühnle, +49 55139 ext. 6201
Recruiting
Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
Greifswald, 17475
Holger Lode, +49 383486 ext. 6325, holger.lode@uni-greifswald.de
Recruiting
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
Hanover, 30625
Christin Linderkamp, +49 511532 ext. 6710, linderkamp.christin@mh-hannover.de
Recruiting
Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
Heidelberg, 69120
Wolfgang Behnisch, +49 622156 ext. 4555, wolfgang.behnisch@med.uni-heidelberg.de
Recruiting
Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
Heilbronn, 74078
Hermann Full, +49 713149 ext. 3702, hermann.full@slk-kliniken.de
Recruiting
Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
Herdecke, 58313
Alfred Längler, +49 233062 ext. 3893, a.laengler@gemeinschaftskrankenhaus.de
Recruiting
Universitaetsklinikum des Saarlandes
Homburg, 66421
Norbert Graf, 49-6841-168-8397
Recruiting
Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
Jena, 7740
Bernd Gruhn, +49 364193 ext. 8220, bernd.gruhn@med.uni-jena.de
Recruiting
Staedtisches Klinikum Karlsruhe gGmbH
Karlsruhe, 76133
A. Leipold, 49-721-9740
Recruiting
Klinikum Kassel
Kassel, D-34125
Michaela Nathrath, MD, 49-561-980-3382
Recruiting
Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
Kiel, 24105
Martin Schrappe, +49 431597 ext. 1620, m.schrappe@pediatrics.uni-kiel.de
Recruiting
Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
Leipzig, 04103
Lars Fischer, 0341-97 26
Recruiting
Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
Lübeck, 23538
Melchior Lauten, +49 451500 ext. 2557, lauten@paedia.ukl.mu-luebeck.de
Recruiting
Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
Magdeburg, 39120
Peter Vorwerk, +49 391671 ext. 7210, peter.vorwerk@med.ovgu.de
Recruiting
Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
Mannheim, 68167
Matthias Dürken, +49 621383 ext. 2244, matthias.duerken@kikli.ma.uni-heidelberg.de
Recruiting
Universitätsklinikum
Mannheim
Matthias Dürken, Dr.
Recruiting
Johannes Wesling Klinikum Minden
Minden, 32429
Bernhard Erdlenbruch, +49 571 ext. 8010, bernhard.erdlenbruch@klinikum-minden.de
Recruiting
Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
München, 80804
Angela Wawer, +49 893068 ext. 2261, angela.wawer@lrz.tum.de
Recruiting
Ludwig-Maximilian-Universität, Dr. von Haunersches Kinderspital
München
Tobias Feuchtinger
Recruiting
Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
Münster, 48149
Claudia Rössig, +49 251834 ext. 5644, rossig@ukmuenster.de
Recruiting
Cnopf'sche Kinderklinik, Onkologie
Nuremberg, 90419
Wolfram Scheurlen, +49 91133 ext. 40323, wolfram.scheurlen@diakonieneudettelsau.de
Recruiting
Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
Oldenburg, 26133
Hermann Müller, +49 441403 ext. 2013, mueller.hermann@klinikum-oldenburg.de
Recruiting
Universitätsklinikum
Regensburg
Selim Corbacioglu, Dr.
Recruiting
Universitäts-Kinderklinik
Rostock, 18055
Carl-Friedrich Classen, +49 381494 ext. 7000, carl-friedrich.classen@med.uni-rostock.de
Recruiting
Asklepios-Klinik, Sankt Augustin GmbH
Sankt Augustin, 53757
Harald Reinhard, +49 224124 ext. 9304, h.reinhard@asklepios.com
Recruiting
HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
Schwerin, 19049
Christian Güttel, +49 385520 ext. 2710, christian.guettel@helios-kliniken.de
Recruiting
Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
Stuttgart, 70176
Stefan Bielack, +49 711992 ext. 2461, st.bielack@olgahospital.de
Recruiting
Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
Trier, 54290
Stefan Weis, +49 651947 ext. 2654, weis@mutterhaus.de
Recruiting
Universitaetsklinikum Tuebingen
Tübingen, D-72076
Martin Ebinger, MD
Recruiting
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Ulm, D-89075
Klaus M. Debatin, MD, 49-731-5000, klaus-michael.debatin@medizin.uni-ulm.de
Recruiting
Stadtkrankenhaus, Kinderklinik
Wolfsburg, 38440
Sally Mukodzi, +49 5361 ext. 8000, sally.mukidzi@klinikum-wolfsburg.de
Recruiting
Universitaets - Kinderklinik Wuerzburg
Würzburg, D-97080
P. G. Schlegel, MD, 49-931-2012-7856, schlegel@mail.uni-wuerzburg.de
Recruiting

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Policlinico Umberto I Università Sapienza di Roma
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A.O.U. Città della salute e della scienza di Torino
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Inselspital Bern
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HUG Hôpitaux Universitaires de Gèneve
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CHUV Centre Hospitalier Universitaire Vaudois
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About this study

Official title: 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.

Read the 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.

Conditions: Acute Lymphoblastic Leukemia, Pediatric
Being tested: Blinatumomab, Bortezomib, Cyclophosphamide, Cytarabine, Daunorubicin
Keywords: Acute Lymphoblastic Leukemia, Childhood, Pediatric, Immunotherapy, Blinatumomab, Proteasome Inhibitor, Bispecific antibody, Bortezomib, Chemotherapy, Randomized trial
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BlinatumomabDrug
Experimental therapy in randomizations R-HR and R-MR
BortezomibDrug
Experimental therapy in randomization R-eHR
CyclophosphamideDrug
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
CytarabineDrug
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
DaunorubicinDrug
Part of standard chemotherapy
MyocetDrug
Part of intensification block Myocet-FLA for patients with very high relapse risk
DexamethasoneDrug
Part of standard chemotherapy
DoxorubicinDrug
Part of standard chemotherapy
EtoposideDrug
Part of standard chemotherapy
Fludarabine PhosphateDrug
Part of intensification block Myocet-FLA for patients with very high relapse risk
IfosfamideDrug
Part of standard chemotherapy
6-MercaptopurineDrug
Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
MethotrexateDrug
Part of standard chemotherapy
PegaspargaseDrug
Part of standard chemotherapy
PrednisoloneDrug
Also called Prednisone
Part of standard chemotherapy
TioguaninDrug
Part of standard chemotherapy
VincristineDrug
Part of standard chemotherapy
VindesineDrug
Part of standard chemotherapy
ErwinaseDrug
Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction

Study groups in NCT03643276
Study group	Role	What they receive
pB: early (non-)HR-standard/MR-standard	Active comparator	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. Receives: 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
pB: early HR-exp./MR-standard	Experimental	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. Receives: Drug: Bortezomib; 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
pB: early (non)HR-standard/MR-exp.	Experimental	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. Receives: Drug: Blinatumomab; 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
pB: early HR-exp./MR-exp.	Experimental	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. Receives: Drug: Blinatumomab; Drug: Bortezomib; 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
pB: early (non-)HR-standard/HR-standard	Active comparator	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). Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Myocet; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Etoposide; Drug: Fludarabine Phosphate; Drug: Ifosfamide; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisolone; Drug: Tioguanin; Drug: Vincristine; Drug: Vindesine; Drug: Erwinase
pB: early HR-exp./HR-standard	Experimental	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) Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Myocet; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Etoposide; Drug: Fludarabine Phosphate; Drug: Ifosfamide; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisolone; Drug: Tioguanin; Drug: Vincristine; Drug: Vindesine; Drug: Erwinase
pB: early (non-)HR-standard/HR-exp.	Experimental	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) Receives: Drug: Blinatumomab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Myocet; Drug: Dexamethasone; Drug: Doxorubicin; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisolone; Drug: Tioguanin; Drug: Vincristine; Drug: Erwinase
pB: early HR-exp./HR-exp.	Experimental	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) Receives: Drug: Blinatumomab; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Myocet; Drug: Dexamethasone; Drug: Doxorubicin; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisolone; Drug: Tioguanin; Drug: Vincristine; Drug: Erwinase
pB: early non-HR/SR	Other	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. Receives: 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
T: early non-SR-standard/(non-)HR	Active comparator	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) Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Myocet; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Etoposide; Drug: Fludarabine Phosphate; Drug: Ifosfamide; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisolone; Drug: Tioguanin; Drug: Vincristine; Drug: Vindesine; Drug: Erwinase
T: early non-SR-exp/(non-)HR	Experimental	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) Receives: Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Myocet; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Etoposide; Drug: Fludarabine Phosphate; Drug: Ifosfamide; Drug: 6-Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Drug: Prednisolone; Drug: Tioguanin; Drug: Vincristine; Drug: Vindesine; Drug: Erwinase
T: early SR/non-HR	Other	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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

Event-free survival
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.
Measured: Assessed up to 120 months from start of study
Disease-free survival
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.
Measured: Assessed up to 120 months from start of study

Secondary outcomes (5)

Survival
All patients/randomizations: Time until death from any cause, starting at the same time point as the EFS/DFS.
Measured: Assessed up to 120 months from start of study
Treatment-related mortality
Frequency and incidence of treatment-related mortality in induction or continuous complete remission
Measured: Assessed up to 120 months from start of study
Adverse Events of interest/Serious Adverse Events
Frequency and incidence of adverse events of interest and serious adverse events in specific protocol phases, randomized arms and overall during follow-up
Measured: Assessed up to 120 months from start of study
MRD response
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)
Measured: 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
Proportion of patients with poor MRD response to the first Blinatumomab cycle ("Blinatumomab Poor-Response") (R-HR)
Measured: Measurements of MRD response intended after 30 weeks from individual start of treatment, assessment of proportion at 120 months from start of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Jul 201814 Jul 2028

First posted22 Aug 2018
Study start15 Jul 2018
Primary completion14 Jul 2028 (estimated)
Study completion14 Jul 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Acute Lymphoblastic Leukemia, PediatricStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Model description: pB-ALL/MR: 2 parallel groups (R-MR) or 2x2 factorial design (R-eHR, R-MR) depending on early risk group assignment. pB-ALL/HR: 2 parallel groups (R-HR) or 2x2 factorial design (R-eHR, R-HR) depending on early risk group assignment. T-ALL/early non-SR: 2 parallel groups (R-T). pB-ALL/SR: Single group. T-ALL/early SR: Single group.
Masking: None (open label)
Enrolment: 5,000 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03643276
Sponsor's protocol ID: AIEOP-BFM ALL 2017
Status last verified: Apr 2025
First submitted: 12 Jul 2018
Last updated: 6 Apr 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Schrappe M, Locatelli F, Valsecchi MG, Zugmaier G, Vossen-Gajcy M, Stary J, Attarbaschi A, Moricke A, Bourquin JP, Barbaric D, Elitzur S, Silvestri D, Kolenova A, Dalla-Pozza L, Bodmer N, Stanulla M, Alten J, Zaman F, Bergmann A, Cazzaniga G, Bruggemann M, Buldini B, Kohler R, Fazio G, Rossig C, Sramkova L, Parasole R, Hundsdorfer P, Putti MC, Borkhardt A, Fagioli F, Bettini LR, Poyer F, von Stackelberg A, Vinti L, Conter V, Zimmermann M, Rizzari C, Cario G, Biondi A; AIEOP-BFM ALL 2017 Consortium. Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia. N Engl J Med. 2026 Sep 17;395(11):1075-1089. doi: 10.1056/NEJMoa2604166.
PubMed 42748428
Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.
PubMed 41671463
Domka K, Dabkowska A, Janowska M, Urbanska Z, Pastorczak A, Winiarska M, Fidyt K, Lachota M, Patkowska E, Sedek L, Perkowski B, Hunia J, Jakubowska J, Krzymieniewska B, Lech-Maranda E, Mlynarski W, Szczepanski T, Firczuk M. Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20+ Philadelphia-positive B-cell precursor acute lymphoblastic leukemia in preclinical models. Haematologica. 2024 Nov 1;109(11):3520-3532. doi: 10.3324/haematol.2023.284853.
PubMed 38841802
Tufekci O, Evim MS, Gunes AM, Celkan T, Karapinar DY, Kaya Z, Baysal B, Baytan B, Kocak U, Yilmaz S, Cinar S, Oren H. Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey. J Pediatr Hematol Oncol. 2022 Mar 1;44(2):e396-e402. doi: 10.1097/MPH.0000000000002419.
PubMed 35129146

Interested in taking part?

Anja Möricke, MD

+4943150020150

a.moericke@pediatrics.uni-kiel.de

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Acute Lymphoblastic Leukemia, Pediatric trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
ClinicalTrials.gov ID: NCT03643276
Acronym / sponsor ID: AIEOP-BFM ALL 2017
Conditions: Acute Lymphoblastic Leukemia, Pediatric
Keywords: Acute Lymphoblastic Leukemia, Childhood, Pediatric, Immunotherapy, Blinatumomab, Proteasome Inhibitor, Bispecific antibody, Bortezomib
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 5,000 participants (estimated)
Lead sponsor: Martin SchrappeUniversity, hospital or other
Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany)
Study start: 15 Jul 2018 (actual)
Primary completion: 14 Jul 2028 (estimated)
Study completion: 14 Jul 2028 (estimated)
First posted: 22 Aug 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The trial includes four randomized study questions testing experimental treatments on top of the risk-stratified standard chemotherapy backbone:

Primary study questions:

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-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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: None (open label)
Number of arms: 12
Model description: pB-ALL/MR: 2 parallel groups (R-MR) or 2x2 factorial design (R-eHR, R-MR) depending on early risk group assignment. pB-ALL/HR: 2 parallel groups (R-HR) or 2x2 factorial design (R-eHR, R-HR) depending on early risk group assignment. T-ALL/early non-SR: 2 parallel groups (R-T). pB-ALL/SR: Single group. T-ALL/early SR: Single group.

Arm	Type	Receives
pB: early (non-)HR-standard/MR-standard	Active comparator	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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.
pB: early HR-exp./MR-standard	Experimental	Drug: Bortezomib, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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.
pB: early (non)HR-standard/MR-exp.	Experimental	Drug: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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.
pB: early HR-exp./MR-exp.	Experimental	Drug: Blinatumomab, Drug: Bortezomib, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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.
pB: early (non-)HR-standard/HR-standard	Active comparator	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Myocet, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Etoposide, Drug: Fludarabine Phosphate, Drug: Ifosfamide, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: Vindesine, Drug: ErwinaseInduction (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).
pB: early HR-exp./HR-standard	Experimental	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Myocet, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Etoposide, Drug: Fludarabine Phosphate, Drug: Ifosfamide, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: Vindesine, Drug: ErwinaseInduction (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)
pB: early (non-)HR-standard/HR-exp.	Experimental	Drug: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Myocet, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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)
pB: early HR-exp./HR-exp.	Experimental	Drug: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Myocet, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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)
pB: early non-HR/SR	Other	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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.
T: early non-SR-standard/(non-)HR	Active comparator	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Myocet, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Etoposide, Drug: Fludarabine Phosphate, Drug: Ifosfamide, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: Vindesine, Drug: ErwinaseInduction (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)
T: early non-SR-exp/(non-)HR	Experimental	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Myocet, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Etoposide, Drug: Fludarabine Phosphate, Drug: Ifosfamide, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: Vindesine, Drug: ErwinaseInduction (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)
T: early SR/non-HR	Other	Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin, Drug: Dexamethasone, Drug: Doxorubicin, Drug: 6-Mercaptopurine, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Tioguanin, Drug: Vincristine, Drug: ErwinaseInduction (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.

Who may qualify

Ages: Up to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (8 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BlinatumomabExperimental therapy in randomizations R-HR and R-MR	Drug	pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early HR-exp./HR-exp., pB: early HR-exp./MR-exp.
BortezomibExperimental therapy in randomization R-eHR	Drug	pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard
CyclophosphamidePart of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
CytarabinePart 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	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
DaunorubicinPart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
MyocetPart of intensification block Myocet-FLA for patients with very high relapse risk	Drug	T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard
DexamethasonePart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
DoxorubicinPart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
EtoposidePart of standard chemotherapy	Drug	T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non-)HR-standard/HR-standard, pB: early HR-exp./HR-standard
Fludarabine PhosphatePart of intensification block Myocet-FLA for patients with very high relapse risk	Drug	T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non-)HR-standard/HR-standard, pB: early HR-exp./HR-standard
IfosfamidePart of standard chemotherapy	Drug	T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non-)HR-standard/HR-standard, pB: early HR-exp./HR-standard
6-MercaptopurinePart of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
MethotrexatePart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
PegaspargasePart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
PrednisoloneAlso: PrednisonePart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
TioguaninPart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
VincristinePart of standard chemotherapy	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR
VindesinePart of standard chemotherapy	Drug	T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non-)HR-standard/HR-standard, pB: early HR-exp./HR-standard
ErwinasePart of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction	Drug	T: early SR/non-HR, T: early non-SR-exp/(non-)HR, T: early non-SR-standard/(non-)HR, pB: early (non)HR-standard/MR-exp., pB: early (non-)HR-standard/HR-exp., pB: early (non-)HR-standard/HR-standard, pB: early (non-)HR-standard/MR-standard, pB: early HR-exp./HR-exp., pB: early HR-exp./HR-standard, pB: early HR-exp./MR-exp., pB: early HR-exp./MR-standard, pB: early non-HR/SR

Primary outcome

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.
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.

5 secondary outcomes

Survival
Time frame: Assessed up to 120 months from start of study
Treatment-related mortality
Time frame: 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
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).
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

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2025.
Derived from this study: PubMed 42748428Schrappe M, Locatelli F, Valsecchi MG, Zugmaier G, Vossen-Gajcy M, Stary J, Attarbaschi A, Moricke A, Bourquin JP, Barbaric D, Elitzur S, Silvestri D, Kolenova A, Dalla-Pozza L, Bodmer N, Stanulla M, Alten J, Zaman F, Bergmann A, Cazzaniga G, Bruggemann M, Buldini B, Kohler R, Fazio G, Rossig C, Sramkova L, Parasole R, Hundsdorfer P, Putti MC, Borkhardt A, Fagioli F, Bettini LR, Poyer F, von Stackelberg A, Vinti L, Conter V, Zimmermann M, Rizzari C, Cario G, Biondi A; AIEOP-BFM ALL 2017 Consortium. Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia. N Engl J Med. 2026 Sep 17;395(11):1075-1089. doi: 10.1056/NEJMoa2604166.
Derived from this study: PubMed 41671463Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067.
Derived from this study: PubMed 38841802Domka K, Dabkowska A, Janowska M, Urbanska Z, Pastorczak A, Winiarska M, Fidyt K, Lachota M, Patkowska E, Sedek L, Perkowski B, Hunia J, Jakubowska J, Krzymieniewska B, Lech-Maranda E, Mlynarski W, Szczepanski T, Firczuk M. Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20+ Philadelphia-positive B-cell precursor acute lymphoblastic leukemia in preclinical models. Haematologica. 2024 Nov 1;109(11):3520-3532. doi: 10.3324/haematol.2023.284853.
Derived from this study: PubMed 35129146Tufekci O, Evim MS, Gunes AM, Celkan T, Karapinar DY, Kaya Z, Baysal B, Baytan B, Kocak U, Yilmaz S, Cinar S, Oren H. Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey. J Pediatr Hematol Oncol. 2022 Mar 1;44(2):e396-e402. doi: 10.1097/MPH.0000000000002419.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Anja Möricke, MD contact

+4943150020150

a.moericke@pediatrics.uni-kiel.de

Lile Bauer contact

+4943150020152

lile.bauer@uksh.de

Martin Schrappe, MD principal investigator

Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel

115 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Blinatumomab, Bortezomib and Cyclophosphamide in people with Acute Lymphoblastic Leukemia, Pediatric, run by Martin Schrappe at 115 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 115 sites in Germany, Italy, Switzerland, Czechia, Israel and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Anja Möricke, MD (+4943150020150, a.moericke@pediatrics.uni-kiel.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (time frame: Assessed up to 120 months from start of study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03643276, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.