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EUCTR2016-001935-12 | SNCTP000003410

Internationales kooperatives Behandlungsprotokoll für Kinder und Jugendliche mit akuter lymphoblastischer Leukämie (ALL)

Data source: BASEC (Imported from 25.02.2020), WHO (Imported from 23.02.2020)
Changed: 20.02.2020
Disease category: Leukämie

Brief description of trial (Source of data: BASEC)

Die akute lymphoblastische Leukämie (kurz ALL) ist die häufigste Art von Blutkrebs im Kindes- und Jugendalter. Die Durchführung von internationalen Studien konnte die Prognose von ALL bereits erheblich verbessern. Es wurden verschiedene Risikofaktoren gefunden, die wichtig für die Heilungsaussichten der Patienten sind.
Patienten mit mehr Risikofaktoren und somit einer höheren Rückfallwahrscheinlichkeit benötigen eine intensivere Therapie, die auch mit mehr Nebenwirkungen verbunden ist. Für Patienten mit weniger Risikofaktoren reicht hingegen eine schwächere Therapie, die mit weniger Nebenwirkungen verbunden ist. Ziel dieser Studie ist es, die bestmögliche Therapie für alle Risikogruppen zu finden. Dies nach dem Prinzip "so viel wie nötig, so wenig wie möglich". Die Therapie sollte somit intensiv genug sein, um Rückfälle der Leukämie zu verhindern, jedoch nicht intensiver als zwingend erforderlich, um Nebenwirkungen bestmöglich zu vermeiden.

Health conditions investigated (Source of data: BASEC)

Akute lymphoblastische Leukämie (ALL)

Health conditions (Source of data: WHO)

acute lymphoblastic leukemia in children and adolescents <18 years of age;Therapeutic area: Diseases [C] - Cancer [C04]

Rare disease (Source of data: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

In dieser Studie werden die Patienten anhand der zuvor erwähnten Risikofaktoren in verschiedene Gruppen mit unterschiedlicher Rückfallwahrscheinlichkeit eingeteilt. Die Einteilung erfolgt aufgrund von Laborergebnissen, welche Informationen über die Eigenschaften der Leukämie jedes einzelnen Patienten liefern. Auch während der Therapie werden diese Eigenschaften weiter untersucht um sicherzustellen, dass jeder Patient in der jeweiligen Therapiephase, nach wie vor der richtigen Gruppe zugeteilt ist.
Die Stärke der Therapie ist dem Rückfallrisiko der Behandlungsgruppe angepasst. In einzelnen Gruppen werden neue Medikamente getestet. Die Patienten erhalten entweder die Standard-Chemotherapie, oder die Standardtherapie zusammen mit neuen Medikamenten. Welcher Patient welche Behandlung erhält wird zufällig entschieden. So können Vor- und Nachteile der neuen Medikamente direkt verglichen und die Therapie für zukünftige Patienten weiter verbessert werden.

Interventions (Source of data: WHO)


Pharmaceutical Form:
INN or Proposed INN: MERCAPTOPURINE
CAS Number: 50-44-2

Pharmaceutical Form:
INN or Proposed INN: TIOGUANINE
CAS Number: 154-42-7

Trade Name: Erwinase
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CRISANTASPASE
CAS Number: 9015-68-3
Current Sponsor code: Erwinase
Other descriptive name: CRISANTASPASE
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 10000-

Trade Name: Oncaspar
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGASPARGASE
CAS Number: 130167-69-0
Current Sponsor code: PEG-Asparaginase
Concentration unit: IU international unit(s)
Concentration type: equal
Concentration number: 3750-

Pharmaceutical Form:
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830-81-3

Pharmaceutical Form:
INN or Proposed INN: PREDNISOLONE
CAS Number: 50-24-8
Other descriptive name: PREDNISOLONE

Pharmaceutical Form:
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Other descriptive name: PREDNISONE

Pharmaceutical Form:
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0

Pharmaceutical Form:
INN or Proposed INN: ETOPOSIDE PHOSPHATE
CAS Number: 117091-64-2
Other descriptive name: ETOPOSIDE PHOSPHATE

Pharmaceutical Form:
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2

Criteria for participation in trial (Source of data: BASEC)

• Erste ALL Diagnose oder erste Diagnose von akuter Leukämie mit spezifischen genetischen Veränderungen (MPAL)
• Patienten unter 18 Jahren zum Zeitpunkt der ALL Diagnose

Exclusion criteria (Source of data: BASEC)

• Schwangerschaft
• Teilnahme an andere klinische Studien
• Krankheit erlaubt keine Behandlung nach dem Protokoll

Inclusion/Exclusion Criteria (Source of data: WHO)

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

Are the trial subjects under 18? yes
Number of subjects for this age range: 5000
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 diseases that does not allow treatment according to the protocol
- 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 that interferes with the protocol

Further information on the trial in WHO primary registry

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001935-12

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2016-001935-12-IT

Further information on trial

Date trial registered

05.11.2018

Incorporation of the first participant

24.01.2019

Recruitment status

Authorised-recruitment may be ongoing or finished

Academic title (Source of data: WHO)

AIEOP-BFM ALL 2017 - International collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia - AIEOP-BFM ALL 2017

Type of trial (Source of data: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Source of data: WHO)


Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
Number of treatment arms in the trial: 14

Phase (Source of data: WHO)

Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Primary end point (Source of data: WHO)

Timepoint(s) of evaluation of this end point: EFS and DFS time: end of study;
Main Objective: - 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 pEFS from time of randomization be improved by additional therapy with the proteasome inhibitor Bortezomib during an extended consolidation treatment phase compared to 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 compared to two conventional highly intensive chemotherapy courses?
(continued in field for another language)
;
Secondary Objective: - 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?
(continued in field for another language)
;
Primary end point(s): For the randomized study questions, the primary endpoint will be the time from randomization until the first event defined as follows:
Randomization R-eHR, R-HR and R-T: 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.
Randomization R-MR: Relapse, second malignancy or death from any cause. This will be called DFS time.

Secundary end point (Source of data: WHO)


Timepoint(s) of evaluation of this end point: Survival, treatment-related mortality, AE and SAE: end of study
MRD related endpoints: after the repective MRD evaluation of the last patient in study
;
Secondary end point(s): - Survival starting at the same time point as the EFS/DFS
- Frequency and incidence of treatment-related mortality in induction or CCR
- Frequency and incidence of AE of interest and SAE in specific protocol phases, randomized arms and overall during follow-up
- MRD load after the randomized treatment phases (R-eHR, R-HR, R-MR and R-T)
- MRD load after the first/second cycle of Blinatumomab or after the HR 2’/HR 3’ block (R-HR)
- Proportion of patients with poor MRD response to the first Blinatumomab cycle (Blinatumomab Poor-Response”) (R HR)

Contact information (Source of data: WHO)

AMGEN

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Aarau, Basel, Bellinzona, Bern, Genf, Lausanne, Luzern, St Gallen, Zürich

Countries (Source of data: WHO)

Australia, Austria, Czech Republic, Germany, Israel, Italy, Slovakia, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

Prof. Dr. med. Felix Niggli
+41 44 266 71 11
felix.niggli@kispi.uzh.ch

Contact for general information (Source of data: WHO)

National Coordinator
Via Pergolesi, 33
Fondazione MBBM- Clinica Pediatrica Università Milano Biccocca
+39039233 6816
aieop-all@unimib.it

Contact for scientific information (Source of data: WHO)

National Coordinator
Via Pergolesi, 33
Fondazione MBBM- Clinica Pediatrica Università Milano Biccocca
+39039233 6816
aieop-all@unimib.it

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

AIEOP- Associazione Italiana Ematologia Oncologia Pediatrica

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2019-00755

Secondary ID (Source of data: WHO)

AIEOP-BFM_ALL_2017;2016-001935-12-DE