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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03643276

Studienbeginn:
Juli 2018

Letztes Update:
29.11.2023

Wirkstoff:
Blinatumomab, Bortezomib, Cyclophosphamide, Cytarabine, Daunorubicin, Myocet, Dexamethasone, Doxorubicin, Etoposide, Fludarabine Phosphate, ifosfamide, 6-mercaptopurine, Methotrexate, Pegaspargase, prednisolone, Tioguanin, Vincristine, Vindesine, Erwinase

Indikation (Clinical Trials):
Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
Phase 3

Sponsor:
Martin Schrappe

Collaborator:
Deutsche Krebshilfe e.V., Bonn (Germany)

Studienleiter

Martin Schrappe, MD
Principal Investigator
Department of Pediatrics, University Hospital of Schleswig-Holstein, Campus Kiel

Kontakt

Studienlocations
(3 von 115)

Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
52074 Aachen
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Udo Kontny
Phone: +49 241808
Phone (ext.): 9902
E-Mail: ukontny@ukaachen.de» Ansprechpartner anzeigen
I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
86156 Augsburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Michael Frühwald
Phone: +49 821400
Phone (ext.): 3631» Ansprechpartner anzeigen
Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Lothar Schweigerer
Phone: +49 309401
Phone (ext.): 2367
E-Mail: lschweigerer@berlin.helio-kliniken.de» Ansprechpartner anzeigen
Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Arend Stackelberg
Phone: +49 30450566
Phone (ext.): 833
E-Mail: arend.stackelberg@charite.de» Ansprechpartner anzeigen
Städtisches Krankenhaus, Kinderklinik
38118 Braunschweig
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Wolfgang Eberl
Phone: +49 531595
Phone (ext.): 1424
E-Mail: w.eberl@klinkum-braunschweig.de» Ansprechpartner anzeigen
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
09009 Chemnitz
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Andre Hofmann
Phone: +49 3713332
Phone (ext.): 4287
E-Mail: a.hofmann@skc.de» Ansprechpartner anzeigen
Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
45711 Datteln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Thomas Wiesel
Phone: +49 236397
Phone (ext.): 5846
E-Mail: th.wiesel@kinderklinik-datteln.de» Ansprechpartner anzeigen
Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
44137 Dortmund
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Dominik Schneider
Phone: +49 2319532
Phone (ext.): 1050
E-Mail: dominik.schneider@klinikumdo.de» Ansprechpartner anzeigen
Centrum für Chronische Immundefizienz des Universitätsklinikums Freiburg
Breisacher Str. 115
79106 Freiburg
(Baden-Württemberg)
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Arndt Borkhardt, Prof.» Ansprechpartner anzeigen
Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
99089 Erfurt
(Thüringen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Axel Sauerbrey
Phone: +49 36178
Phone (ext.): 4501
E-Mail: axel.sauerbrey@helios-kliniken.de» Ansprechpartner anzeigen
Klinikum der J.W. Goethe Universitaet
D-60590 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Thomas Klingebiel, MD
Phone: 49-69-6301-5094
E-Mail: thomas.klingebiel@kgu.de» Ansprechpartner anzeigen
Universitaetskinderklinik - Universitaetsklinikum Freiburg
D-79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Charlotte Niemeyer, MD
Phone: 49-761-270-4506
E-Mail: charlotte.niemeyer@uniklinik-freiburg.de» Ansprechpartner anzeigen
Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
35385 Gießen
(Hessen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christine Mauz-Körholz» Ansprechpartner anzeigen
Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
17475 Greifswald
(Mecklenburg-Vorpommern)
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Ansprechpartner:
Holger Lode
Phone: +49 383486
Phone (ext.): 6325
E-Mail: holger.lode@uni-greifswald.de» Ansprechpartner anzeigen
Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
37099 Göttingen
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ingrid Kühnle
Phone: +49 55139
Phone (ext.): 6201» Ansprechpartner anzeigen
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
30625 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Christin Linderkamp
Phone: +49 511532
Phone (ext.): 6710
E-Mail: linderkamp.christin@mh-hannover.de» Ansprechpartner anzeigen
Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Wolfgang Behnisch
Phone: +49 622156
Phone (ext.): 4555
E-Mail: wolfgang.behnisch@med.uni-heidelberg.de» Ansprechpartner anzeigen
Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
74078 Heilbronn
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Hermann Full
Phone: +49 713149
Phone (ext.): 3702
E-Mail: hermann.full@slk-kliniken.de» Ansprechpartner anzeigen
Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
58313 Herdecke
(Nordrhein-Westfalen)
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Ansprechpartner:
Alfred Längler
Phone: +49 233062
Phone (ext.): 3893
E-Mail: a.laengler@gemeinschaftskrankenhaus.de» Ansprechpartner anzeigen
Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
7740 Jena
(Thüringen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Bernd Gruhn
Phone: +49 364193
Phone (ext.): 8220
E-Mail: bernd.gruhn@med.uni-jena.de» Ansprechpartner anzeigen
IBZ - Interdisziplinäres Brustzentrum am Klinikum Kassel
Mönchebergstraße 41-43
34125 Kassel
(Hessen)
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Ansprechpartner:
Michaela Nathrath, MD
Phone: 49-561-980-3382» Ansprechpartner anzeigen
Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
24105 Kiel
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Martin Schrappe
Phone: +49 431597
Phone (ext.): 1620
E-Mail: m.schrappe@pediatrics.uni-kiel.de» Ansprechpartner anzeigen
Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
50735 Köln
(Nordrhein-Westfalen)
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Ansprechpartner:
Aram Prokop
Phone: +49 2218907
Phone (ext.): 5158
E-Mail: prokopa@klinken-koeln.de» Ansprechpartner anzeigen
Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
50937 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Thorsten Simon
Phone: +49 221478
Phone (ext.): 4380
E-Mail: thorsten.simon@uk-koeln.de» Ansprechpartner anzeigen
Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
04103 Leipzig
(Sachsen)
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Ansprechpartner:
Lars Fischer
Phone: 0341-97 26» Ansprechpartner anzeigen
Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
23538 Lübeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Melchior Lauten
Phone: +49 451500
Phone (ext.): 2557
E-Mail: lauten@paedia.ukl.mu-luebeck.de» Ansprechpartner anzeigen
Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
39120 Magdeburg
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Peter Vorwerk
Phone: +49 391671
Phone (ext.): 7210
E-Mail: peter.vorwerk@med.ovgu.de» Ansprechpartner anzeigen
Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Matthias Dürken
Phone: +49 621383
Phone (ext.): 2244
E-Mail: matthias.duerken@kikli.ma.uni-heidelberg.de» Ansprechpartner anzeigen
Centrum für Chronische Immundefizienz des Universitätsklinikums Freiburg
Breisacher Str. 115
79106 Freiburg
(Baden-Württemberg)
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Matthias Dürken, Dr.» Ansprechpartner anzeigen
Johannes Wesling Klinikum Minden
32429 Minden
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Bernhard Erdlenbruch
Phone: +49 571
Phone (ext.): 8010
E-Mail: bernhard.erdlenbruch@klinikum-minden.de» Ansprechpartner anzeigen
Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
80804 München
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Angela Wawer
Phone: +49 893068
Phone (ext.): 2261
E-Mail: angela.wawer@lrz.tum.de» Ansprechpartner anzeigen
Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
48149 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Claudia Rössig
Phone: +49 251834
Phone (ext.): 5644
E-Mail: rossig@ukmuenster.de» Ansprechpartner anzeigen
Cnopf'sche Kinderklinik, Onkologie
90419 Nürnberg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Wolfram Scheurlen
Phone: +49 91133
Phone (ext.): 40323
E-Mail: wolfram.scheurlen@diakonieneudettelsau.de» Ansprechpartner anzeigen
Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
26133 Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Hermann Müller
Phone: +49 441403
Phone (ext.): 2013
E-Mail: mueller.hermann@klinikum-oldenburg.de» Ansprechpartner anzeigen
Centrum für Chronische Immundefizienz des Universitätsklinikums Freiburg
Breisacher Str. 115
79106 Freiburg
(Baden-Württemberg)
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Selim Corbacioglu, Dr.» Ansprechpartner anzeigen
Universitäts-Kinderklinik
18055 Rostock
(Mecklenburg-Vorpommern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Carl-Friedrich Classen
Phone: +49 381494
Phone (ext.): 7000
E-Mail: carl-friedrich.classen@med.uni-rostock.de» Ansprechpartner anzeigen
Asklepios-Klinik, Sankt Augustin GmbH
53757 Sankt Augustin
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Harald Reinhard
Phone: +49 224124
Phone (ext.): 9304
E-Mail: h.reinhard@asklepios.com» Ansprechpartner anzeigen
HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
19049 Schwerin
(Mecklenburg-Vorpommern)
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Ansprechpartner:
Christian Güttel
Phone: +49 385520
Phone (ext.): 2710
E-Mail: christian.guettel@helios-kliniken.de» Ansprechpartner anzeigen
Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
70176 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Stefan Bielack
Phone: +49 711992
Phone (ext.): 2461
E-Mail: st.bielack@olgahospital.de» Ansprechpartner anzeigen
Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
54290 Trier
(Rheinland-Pfalz)
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Ansprechpartner:
Stefan Weis
Phone: +49 651947
Phone (ext.): 2654
E-Mail: weis@mutterhaus.de» Ansprechpartner anzeigen
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
D-89075 Ulm
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Klaus M. Debatin, MD
Phone: 49-731-5000
E-Mail: klaus-michael.debatin@medizin.uni-ulm.de» Ansprechpartner anzeigen
Stadtkrankenhaus, Kinderklinik
38440 Wolfsburg
(Niedersachsen)
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Ansprechpartner:
Sally Mukodzi
Phone: +49 5361
Phone (ext.): 8000
E-Mail: sally.mukidzi@klinikum-wolfsburg.de» Ansprechpartner anzeigen
Universitaets - Kinderklinik Wuerzburg
D-97080 Wuerzburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
P. G. Schlegel, MD
Phone: 49-931-2012-7856
E-Mail: schlegel@mail.uni-wuerzburg.de» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. 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.

2. 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.

Secondary outcome:

1. 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.

2. 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

3. 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

4. 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)

5. 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)

Studien-Arme

  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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)
  • 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)
  • 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)
  • 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.
  • 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)
  • 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)
  • 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.

Geprüfte Regime

  • Blinatumomab:
    Experimental therapy in randomizations R-HR and R-MR
  • Bortezomib:
    Experimental therapy in randomization R-eHR
  • Cyclophosphamide:
    Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
  • Cytarabine:
    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
  • Daunorubicin:
    Part of standard chemotherapy
  • Myocet:
    Part of intensification block Myocet-FLA for patients with very high relapse risk
  • Dexamethasone:
    Part of standard chemotherapy
  • Doxorubicin:
    Part of standard chemotherapy
  • Etoposide:
    Part of standard chemotherapy
  • Fludarabine Phosphate:
    Part of intensification block Myocet-FLA for patients with very high relapse risk
  • Ifosfamide:
    Part of standard chemotherapy
  • 6-Mercaptopurine:
    Part of standard chemotherapy and included in experimental treatment phase Protocol IB long in randomization R-T
  • Methotrexate:
    Part of standard chemotherapy
  • Pegaspargase:
    Part of standard chemotherapy
  • Prednisolone (Prednisone):
    Part of standard chemotherapy
  • Tioguanin:
    Part of standard chemotherapy
  • Vincristine:
    Part of standard chemotherapy
  • Vindesine:
    Part of standard chemotherapy
  • Erwinase:
    Part of standard chemotherapy as substitute for PEG-L-Asparaginase in case of allergic reaction

Quelle: ClinicalTrials.gov


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