Summary

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.

Recruiting in the following locations

US States None

Other countries Australia, Austria, Czechia, Germany, Israel, Italy, Slovakia, Switzerland

Sydney Children's Hospital

Sydney, Australia Recruiting

The Children's Hospital at Westmead

Westmead, Australia Recruiting

Univ.Klinik für Kinder- und Jugendheilkunde Graz

Graz, Austria Recruiting

Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck

Innsbruck, Austria Recruiting

Kepler Universitätsklinikum

Linz, Austria Recruiting

LKH Salzburg

Salzburg, Austria Recruiting

St. Anna Kinderspital

Vienna, Austria Recruiting

University Hospital Brno

Brno, Czechia Recruiting

University Hospital Hradec Králové

Hradec Králové, Czechia Recruiting

University Hospital Olomouc

Olomouc, Czechia Recruiting

University Hospital Ostrava-Poruba

Ostrava-Poruba, Czechia Recruiting

University Hospital Plzeň

Plzeň, Czechia Recruiting

University Hospital Motol

Praha, Czechia Recruiting

Masaryk´s Hospital Ústí nad Labem

Ústí nad Labem, Czechia Recruiting

Regional Hospital České Budějovice

České Budějovice, Czechia Recruiting

Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie

Aachen, Germany Recruiting

I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie

Augsburg, Germany Recruiting

Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie

Berlin, Germany Recruiting

Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie

Berlin, Germany Recruiting

Städtisches Krankenhaus, Kinderklinik

Braunschweig, Germany Recruiting

Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie

Chemnitz, Germany Recruiting

Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie

Cottbus, Germany Recruiting

Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke

Datteln, Germany Recruiting

Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin

Dortmund, Germany Recruiting

Universitatsklinikum Carl Gustav Carus

Dresden, Germany Recruiting

Universitätsklinik

Düsseldorf, Germany Recruiting

Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde

Erfurt, Germany Recruiting

Universitaets - Kinderklinik

Erlangen, Germany Recruiting

Universitaetsklinikum Essen

Essen, Germany Recruiting

Klinikum der J.W. Goethe Universitaet

Frankfurt, Germany Recruiting

Universitaetskinderklinik - Universitaetsklinikum Freiburg

Freiburg, Germany Recruiting

Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie

Gießen, Germany Recruiting

Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische
Onkologie und Hämatologie

Greifswald, Germany Recruiting

Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie

Göttingen, Germany Recruiting

Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin

Hannover, Germany Recruiting

Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie

Heidelberg, Germany Recruiting

Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum

Heilbronn, Germany Recruiting

Gemeinschaftskrankenhaus Herdecke, Kinderabteilung

Herdecke, Germany Recruiting

Universitaetsklinikum des Saarlandes

Homburg, Germany Recruiting

Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin

Jena, Germany Recruiting

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, Germany Recruiting

Klinikum Kassel

Kassel, Germany Recruiting

Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel

Kiel, Germany Recruiting

Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl

Köln, Germany Recruiting

Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-
hämatologische Station

Köln, Germany Recruiting

Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und
Hämostaseologie

Leipzig, Germany Recruiting

Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie

Lübeck, Germany Recruiting

Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie

Magdeburg, Germany Recruiting

Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie

Mannheim, Germany Recruiting

Universitätsklinikum

Mannheim, Germany Recruiting

Johannes Wesling Klinikum Minden

Minden, Germany Recruiting

Ludwig-Maximilian-Universität, Dr. von Haunersches Kinderspital

München, Germany Recruiting

Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU

München, Germany Recruiting

Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie

Münster, Germany Recruiting

Cnopf'sche Kinderklinik, Onkologie

Nürnberg, Germany Recruiting

Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)

Oldenburg, Germany Recruiting

Universitätsklinikum

Regensburg, Germany Recruiting

Universitäts-Kinderklinik

Rostock, Germany Recruiting

Asklepios-Klinik, Sankt Augustin GmbH

Sankt Augustin, Germany Recruiting

HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin

Schwerin, Germany Recruiting

Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie

Stuttgart, Germany Recruiting

Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung

Trier, Germany Recruiting

Universitaetsklinikum Tuebingen

Tuebingen, Germany Recruiting

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, Germany Recruiting

Stadtkrankenhaus, Kinderklinik

Wolfsburg, Germany Recruiting

Universitaets - Kinderklinik Wuerzburg

Wuerzburg, Germany Recruiting

Soroka University Medical Center

Beer Sheva, Israel Recruiting

Rambam Health Care Campus

Haifa, Israel Recruiting

Hadassah Medical center

Jerusalem, Israel Recruiting

Schneider Children Medical Center of Israel

Petach-Tikva, Israel Recruiting

Sheba Medical Center Tel-Hashomer

Ramat Gan, Israel Recruiting

Dana children hospital

Tel-Aviv, Israel Recruiting

Azienda ospedali riuniti

Ancona, Italy Recruiting

AOUC Policlinico Bari

Bari, Italy Recruiting

A.O. Papa Giovanni XXIII

Bergamo, Italy Recruiting

Università di Bologna

Bologna, Italy Recruiting

ASST Spedali Civili di Brescia

Brescia, Italy Recruiting

Ospedale Businco

Cagliari, Italy Recruiting

Azienda ospedaliero universitaria

Catania, Italy Recruiting

AO Pugliese Ciaccio

Catanzaro, Italy Recruiting

S.O. Annunziata - A. O. Cosenza

Cosenza, Italy Recruiting

Ospedale Meyer

Firenze, Italy Recruiting

Istituto Giannina Gaslini

Genova, Italy Recruiting

Policlinico di Modena Azienda Ospedaliero-Universitaria

Modena, Italy Recruiting

Clinica pediatrica Fondazione MBBM

Monza, Italy Recruiting

A.O.U. Vanvitelli

Napoli, Italy Recruiting

AORN Santobono Pausilipon

Napoli, Italy Recruiting

Azienda ospedaliera di Padova

Padova, Italy Recruiting

Ospedale Civico ARNAS Civico e Di Cristina

Palermo, Italy Recruiting

Azienda ospedaliero-universitaria di Parma

Parma, Italy Recruiting

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy Recruiting

Ospedale S. Maria della misericordia

Perugia, Italy Recruiting

Ospedale Civile di Pescara

Pescara, Italy Recruiting

Ospedale Santa Chiara Pisa

Pisa, Italy Recruiting

Grande ospedale metropolitano B-M-M

Reggio Calabria, Italy Recruiting

Ospedale infermi

Rimini, Italy Recruiting

Fondazione Policlinico Gemelli

Roma, Italy Recruiting

Ospedale Bambino Gesù

Roma, Italy Recruiting

Policlinico Umberto I Università Sapienza di Roma

Roma, Italy Recruiting

Ospedale "Casa sollievo della sofferenza"

San Giovanni Rotondo, Italy Recruiting

A.O.U. Città della salute e della scienza di Torino

Torino, Italy Recruiting

IRCCS Burlo Garofolo

Trieste, Italy Recruiting

AOU Verona

Verona, Italy Recruiting

Klinika pediatrickej hematológie a onkológie SZU a DFNsP

Banská Bystrica, Slovakia Recruiting

Comenius University Children's Hospital

Bratislava, Slovakia Recruiting

Detská fakultná nemocnica Košice

Košice, Slovakia Recruiting

Kantonsspital Aarau

Aarau, Switzerland Recruiting

Universitäts-Kinderspital beider Basel

Basel, Switzerland Recruiting

Ospedale San Giovanni Bellinzona

Bellinzona, Switzerland Recruiting

Inselspital Bern
Bern, Switzerland Recruiting

HUG Hôpitaux Universitaires de Gèneve

Genève, Switzerland Recruiting

CHUV Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland Recruiting

Luzerner Kantonsspital-Kinderspital Luzern

Luzern, Switzerland Recruiting

Ostschweizer Kinderspital

St. Gallen, Switzerland Recruiting

Universitäts-Kinderspital Zürich

Zürich, Switzerland Recruiting

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

Trial information was received from ClinicalTrials.gov and was last updated on

July 5, 2022. This information was provided to ClinicalTrials.gov by University
Hospital Schleswig-Holstein on July 6, 2021.