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SNCTP000003424 | EUCTR2017-000705-20 | BASEC2019-01172

Eine internationale Phase 3 Studie für Philadelphia Chromosom-positive akute lymphoblastische Leukämie (Ph+ ALL), die Imatinib in Kombination mit zwei verschiedenen zytotoxischen Chemotherapien untersucht.

Data source: BASEC (Imported from 11.10.2024), WHO (Imported from 09.10.2024)
Changed: Sep 27, 2024, 1:00 AM
Disease category: Leukemia

Brief description of trial (Data source: BASEC)

Ph+ ALL ist eine bei Kindern und Jugendlichen seltene Blutkrebserkrankung, die den ganzen Körper betrifft. Bei der Krankheit handelt es sich um eine akute lymphoblastische Leukämie (ALL), die eine spezifische genetische Veränderung aufweist, welche Philadelphia-Chromosom genannt wird. Aufgrund dieser Veränderung ist auch eine spezielle Behandlung notwendig. Das Ziel dieser Studie ist es, die Behandlung von Ph+ ALL Patienten zu verbessern. Um die Nebenwirkungen der Behandlung der Ph+ ALL so gering wie möglich zu halten, wird einerseits versucht, die Behandlungsstärke und -dauer so niedrig wie möglich zu halten. Andererseits soll jedoch jedes Kind so viel und so lange eine Behandlung erhalten, dass die Leukämie überwunden werden kann und nicht mehr wiederkehrt. Um diesen beiden unterschiedlichen Zielen bei jedem Patienten möglichst gut gerecht werden zu können, erfolgt die Behandlung dem jeweiligen Rückfallsrisiko angepasst in sogenannten Risikogruppen. Rückfallsrisiko bedeutet dabei das Risiko, dass der Krebs nach der Behandlung wieder zurückkommt. Bei der Ph+ ALL hat sich in vorangegangenen Studien eine Einteilung in Risikogruppen anhand des Ansprechens der Leukämiezellen auf die vorangehende Therapie als sehr sinnvoll erwiesen.

Health conditions investigated(Data source: BASEC)

Philadelphia Chromosom-positive akute lymphoblastische Leukämie (Ph+ ALL) und 'Philadelphia like' ALL

Health conditions (Data source: WHO)

Philadelphia positive Acute Lumphoblastic Leukemia
MedDRA version: 21.0Level: PTClassification code 10034877Term: Philadelphia chromosome positiveSystem Organ Class: 10022891 - Investigations
MedDRA version: 21.0Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 100000004864;Therapeutic area: Diseases [C] - Cancer [C04]

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Das Therapieprogramm besteht aus zwei Teilen. Die Anfangsphase der Ph+ ALL Behandlung wird Induktion genannt. Sie stellt eine Kombination aus mehreren Chemotherapie-Medikamenten dar, die darauf abzielt, möglichst alle Leukämiezellen abzutöten. Während diesem Teil werden Informationen über den Krankheitsverlauf und das Ansprechen auf die Behandlung gesammelt und ausgewertet. Nach Abschluss der Induktionstherapie werden die Patienten je nach Ansprechen der Leukämiezellen auf die Behandlung in zwei Risikogruppen eingeteilt und die weitere Therapie auf das jeweilige Risiko eines Rückfalls der Erkrankung abgestimmt. Dazu werden nach der ersten Therapiephase die Anzahl verbleibender Leukämiezellen im Knochenmark gemessen:

1) Falls nach der Induktion keine oder nur wenige Leukämiezellen nachgewiesen werden können, wird der Patient in die Standardrisikogruppe eingeteilt. Hier wird untersucht, ob eine weniger intensive Chemotherapie in Kombination mit dem Medikament Imatinib gleich wirksam ist, wie die bis heute angewandte stärkere Standardchemotherapie ebenfalls in Kombination mit Imatinib. Die Studie soll herausfinden, ob Patienten auch mit dem Prüfarm, in dem weniger Nebenwirkungen (d.h. insbesondere weniger lebensbedrohliche Infektionen, weniger Therapiepausen und weniger Spätfolgen) zu erwarten sind als im intensiven Standardarm, geheilt werden können. Da zurzeit nicht bekannt ist, welche Behandlung für die Patienten besser ist, erfolgt die Therapiezuteilung zufällig.

2) Patienten, bei denen noch mässig bis deutlich hohe Reste an Leukämiezellen gefunden wurden, werden der Hochrisikogruppe zugeordnet. Der zweite Therapieteil dieser Risikogruppe plant zusätzlich zur intensiven Standardchemotherapie eine Stammzelltransplantation. Grund dafür ist, dass die Heilungschancen mit einer Stammzelltransplantation über jenen einer alleinigen Chemotherapie liegen. Bei Patienten mit hohem Rückfallrisiko wird zusätzlich untersucht, ob die standardisierte Gabe von Imatinib nach der erfolgten Stammzelltransplantation zum einen machbar ist und zum anderen die Prognose verbessert.

Um dies korrekt und in allen Details zu studieren, wird in der Studie einerseits eine standardisierte Diagnostik in sogenannten Referenzlaboren durchgeführt, und andererseits werden von allen teilnehmenden Patienten medizinische Daten erfasst, gespeichert und gemeinsam ausgewertet. Zusätzlich werden Forschungsprojekte durchgeführt, um die Biologie der Ph+ ALL bei Kindern immer besser zu verstehen und um neue Wege der Diagnostik und Behandlung zu erforschen.

Interventions (Data source: WHO)


Trade Name: DECADRON
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Current Sponsor code: DEX
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0.5-.075

Trade Name: DELTACORTENE
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Current Sponsor code: PDN
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-25

Trade Name: VINCRISTINA TEVA
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: VINCRISTINE
CAS Number: 57-22-7
Current Sponsor code: VCR
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: DAUNOBLASTINA
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830-81-3
Current Sponsor code: DAUN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: DOXORUBICINA TEVA
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DOXORUBICIN HYDROCHLORIDE
Current Sponsor code: DOXO
Other descriptive name: DOXORUBICIN HYDROCHLORIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: ENDOXAN BAXTER
Pharmaceutical Form: Powder for solution for injection/infusion
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Current Sponsor code: CPM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: ARACYTIN
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: CYTARABINE
Current Sponsor code: ARA-C
Other descriptive name: CYTARABINE
Concentration unit: mg milligram(s)
C

Criteria for participation in trial (Data source: BASEC)

Erste ALL Diagnose (T-Zellen oder B-Zellen) mit spezifischen genetischen Veränderungen
Patienten zwischen 1 und 17 Jahren zum Zeitpunkt der ALL Diagnose

Exclusion criteria (Data source: BASEC)

Chronische myeloische Leukämie (CML)
Sekundäre ALL in Folge der Behandlung einer anderen Krebsart

Inclusion/Exclusion Criteria (Data source: WHO)

Gender:
Female: yes
Male: yes

Inclusion criteria:
1. Patients should be enrolled on National ALL protocol prior to
enrollment on EsPhALL2017/COGAALL1631. Regardless of initial frontline
protocol baseline diagnostic samples must be available to develop
an MRD probe.
Diagnostic samples will be collected and analyzed according to the
procedures of the National front-line protocol.
2. > 1 year and < 21 years at ALL diagnosis
3. New LLA diagnosis
a. type B or T, or mixed phenotypic acute leukemia (MPAL meeting 2016
WHO definition) with definitive evidence of BCR-ABL1 fusion by
karyotype, FISH and/or RT-PCR
b. type B, with definitive evidence of ABL class fusions identified
according to National/Center procedures of each participating country.
4. Prior Therapy for BCR-ABL1 fusion patients:
a. induction therapy, which includes vincristine, a corticosteroid, usually
PEG-L-Asparaginase, with or without anthracycline, and/or other
standard cytotoxic chemotherapy.
b. Not received more than 14 days of multiagent induction therapy
beginning with the first dose of vincristine.
c. May have started imatinib prior to study entry but have not received
more than 14 days of imatinib.
5. Prior Therapy for ABL-class fusion patients:
a. must have previously completed the 4 or 5 weeks of multiagent
Induction chemotherapy.
b. may have started imatinib during Induction IA, at the same time of or
after the first vincristine dose.
6. Patients must have a performance status corresponding to ECOG
scores of 0, 1, or 2.
7. Adequate liver function.
8. Adequate cardiac function.
9. Adequate renal function.


Are the trial subjects under 18? yes
Number of subjects for this age range: 630
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Known history of chronic myelogenous leukemia (CML).
2.ALL developing after a previous cancer treated with cytotoxic chemotherapy.
3.Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation.
4.Down syndrome.
5.Pregnancy.
6.Breast feeding.
7.Patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
8.Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block.
9.Prior treatment with dasatinib, or any BCR-ABL1 inhibitor other than imatinib.

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2017-000705-20
Further information on trial

Date trial registered

Dec 4, 2019

Incorporation of the first participant

Mar 19, 2020

Recruitment status

Authorised-recruitment may be ongoing or finished

Academic title (Data source: WHO)

International phase 3 trial in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) testing imatinib in combination with two different cytotoxic chemotherapy backbones - EsPhALL2017/COGAALL1631

Type of trial (Data source: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Data source: 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: no Placebo: no Other: yes Other specify the comparator: two different chemotheraphy Number of treatment arms in the trial: 2

Phase (Data source: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primary end point (Data source: WHO)

Main Objective: To compare disease-free survival (DFS) of Standard Risk (SR) pediatric Ph+ ALL patients treated with continuous imatinib combined with either a high risk COG ALL Chemotherapy backbone or the more intensive the EsPhALL chemotherapy backbone;Secondary Objective: 1. To compare disease free survival (DFS) of SR pediatric Ph+ and ABLclass
fusion positive ALL patients treated with continuous imatinib
combined with either a high-risk COG-ALL chemotherapy backbone or
the more intensive EsPhALL chemotherapy backbone.
To determine the feasibility of administration of imatinib after allogeneic
HSCT in High Risk (HR) Ph+ ALL patients.
2. To determine event-free-survival (EFS) of HR pediatric Ph+ ALL
patients treated with EsPhALL chemotherapy, HSCT in first complete
remission and post-HSCT imatinib.
3. To compare rates of Grade 3 or higher infections in SR Ph+ ALL
patients between the two randomized arms.
4. To evaluate EFS and overall survival (OS) of all eligible Ph+ALL
patients enrolled on the study.
5. To evaluate OS in SR Ph+ ALL patients.
6. To evaluate OS in HR Ph+ ALL patients.
7. To evaluate EFS and OS of all eligible ABL-class fusion positive ALL
patients enrolled on the study.
;Primary end point(s): DFS, defined as the time from randomization to first event (relapse, second malignancy, or death in complete remission) or time to last follow-up for patients without events.;Timepoint(s) of evaluation of this end point: from randomization to first event (relapse, second malignancy, or death in complete remission) or time to last follow-up for patients without events.

Secundary end point (Data source: WHO)

Secondary end point(s): 1. To compare disease free survival (DFS) of SR pediatric Ph+ and ABLclass
fusion positive patients treated with continuous imatinib combined
with either a high-risk COG-ALL chemotherapy backbone or the more
intensive EsPhALL chemotherapy backbone. The DFS is defined as the
time from randomization to first event (relapse, second malignancy, or
death in complete remission) or time to last follow-up for patients
without events. DFS comparison will be done according to the intention
to treat (ITT) principle by assigned arm. Since only limited data will be
available for ABL-class fusion positive patients, applicability of the
pooled analysis to this subgroup is questionable. A separate analysis for
the ABL-class fusion positive patients is therefore planned as exploratory
aim.
2. To determine the feasibility of administration of imatinib after
allogeneic HSCT in HR Ph+ ALL patients.
3. To determine event free survival (EFS) of HR pediatric Ph+ ALL
patients treated with EsPhALL chemotherapy, HSCT in first complete
remission and post-HSCT imatinib. EFS is defined as the time from the
date of bone marrow for MRD assessment at end-IB to first event
(resistant disease [i.e. MRD=10^-2 or morphologic residual disease at
end of Consolidation Block 3], relapse, progressive disease [i.e. MRD =
10^-2 at two post-HSCT time points separated by at least 2 weeks
obtained at Day 90 or later from HSCT], second malignancy, or death in
complete remission) or time to last follow-up for patients without
events.
4. To compare rates of Grade 3 or higher infections in Standard Risk Ph+
ALL patients between the two randomized arms.
5. To evaluate EFS and overall survival (OS) of all eligible Ph+ ALL
patients enrolled on the study.
6. To evaluate OS in SR Ph+ ALL patients. OS as secondary endpoint is
defined as the time from randomization to death from any cause.
7. To evaluate OS (defined as time from MRD assessment at end-IB to
death from any cause) in HR Ph+ ALL.
8. To evaluate EFS and OS of all eligible ABL-class fusion positive ALL
patients enrolled on the study.;Timepoint(s) of evaluation of this end point: 1.From day +56 to +365
2.from the date of bone marrow for MRD assessment at end-IB to first event or time to last follow-up for patients without events.
3.From the end of IB to the start of Manteinance
4.EFS: from enrollment until the first occurrence of M3 marrow at the end of Induction IA, relapse, second malignancy, or death as a first event); OS: from the time from study enrollment to death from any cause.
5.From enrollment to death from any cause.
6.From MRD assessment at end-IB to death from any cause.

Contact information (Data source: WHO)

Universit? degli Studi Milano Bicocca

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Aarau, Basel, Bellinzona, Bern, Geneva, Lausanne, Luzern, St. Gallen, Zurich

Countries (Data source: WHO)

Australia, Austria, Belgium, Canada, Chile, Czech Republic, Czechia, Denmark, European Union, Finland, France, Germany, Hong Kong, Israel, Italy, Netherlands, Poland, Sweden, Switzerland, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Dr. med. Nicole Bodmer
+41 44 266 74 55
nicole.bodmer@kispi.uzh.ch

Contact for general information (Data source: WHO)

Anne Uyttebroeck
Herestraat 49
UZ Leuven
anne.uyttebroeck@uzleuven.be

Contact for scientific information (Data source: WHO)

Anne Uyttebroeck
Herestraat 49
UZ Leuven
anne.uyttebroeck@uzleuven.be

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

20.08.2019

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2019-01172

Secondary ID (Data source: WHO)

EsPhALL2017/COGAALL1631
2017-000705-20-AT
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