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 or ABL1 class 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: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);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)
Pharmaceutical Form:
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Current Sponsor code: DEX
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0,5-1
Pharmaceutical Form:
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Current Sponsor code: DEX
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0,5-1
Pharmaceutical Form:
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: equal
Concentration number: 5-
Pharmaceutical Form:
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: equal
Concentration number: 5-
Pharmaceutical Form:
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-
Pharmaceutical Form:
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: CERUBIDINE 20 mg, poudre pour solution pour perfusion
Pharmaceutical Form:
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: 5-
Trade Name: CERUBIDINE 20 mg, poudre pour solution pour perfusion
Pharmaceutical Form:
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: 5-
Pharmaceut
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.Enrollment on National ALL protocol.
2.Age > 1 year and < 21 years at ALL diagnosis.
3. BCR-ABL1 fusion: newly diagnosed ALL (B-ALL or T-ALL) or mixed
phenotypic acute leukemia
4. ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABLclass fusions
5. BCR-ABL1 patients must have previously started Induction therapy, which includes vincristine, a corticosteroid, usually PEG-L-Asparaginase, with or without anthracycline, and/or other standard cytotoxic chemotherapy.
6. BCR-ABL1 patients have not received more than 14 days of multiagent Induction therapy beginning with the first dose of vincristine.
7. BCR-ABL1 patients may have started imatinib prior to study entry but have
not received more than 14 days of imatinib.
8. ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy.
9. ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vincristine dose.
10.Performance status corresponding to ECOG scores of 0, 1, or 2.
11.Adequate liver function.
12.Adequate cardiac function.
13.Adequate renal function.
3.Newly diagnosed ALL (B-ALL or T-ALL)or mixed phenotypic acute leukemia (MPAL meeting 2016 WHO definition) with definitive evidence of BCR-ABL1 fusion by karyotype, FISH and/or RT-PCR.
4.Previous start of Induction therapy which includes vincristine, a corticosteroid, usually PEG-L-Asparaginase, with or without anthracycline, and/or other standard cytotoxic chemotherapy.
5.Administration of no more than 14 days of multiagent Induction therapy beginning with the first dose of vincristine.
6.Administration of no more than 14 days of imatinib.
7.Performance status corresponding to ECOG scores of 0, 1, or 2.
8.Adequate liver function.
9.Adequate cardiac function.
10.Adequate renal function.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
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:
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 treatment according to protocol.
8.Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block.
9.Prior treatment with dasatinib, or any TKI inhibitor other than imatinib.
-
Further information on trial
Date trial registered
Oct 7, 2020
Incorporation of the first participant
Mar 1, 2021
Recruitment status
Not Recruiting
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: Por?wnanie czasu przezycia wolnego od nawrotu choroby (DFS) w populacji pediatrycznej Ph+ ALL z grupy standardowego ryzyka (SR) leczonej ciaglym imatynibem, w polaczeniu ze schematem chemioterapii wysokiego ryzyka COG ALL badz bardziej intensywna chemioterapia schematu EsPhALL.
;Secondary Objective: 1. To compare disease free survival (DFS) of SR pediatric Ph+ and ABL-class 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.
2. To determine the feasibility of administration of imatinib after allogeneic HSCT in
High Risk (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.
4. To compare rates of Grade 3 or higher infections in SR 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.
7. To evaluate OS in HR Ph+ ALL patients.
8. To evaluate EFS and OS of all eligible ABL-class fusion positive ALL patients
enrolled on the study.;Primary end point(s): To compare disease free survival (DFS) of SR pediatric Ph+ ALL patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.;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 ABL-class fusion positive patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
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 ormorphologic 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.The DFS is defined as the time from randomization to first event (relapse, second malignancy, or death in CR) or time to last f/u for patients without events
1.From day +56 to +365
2.from the date of BM for MRD assessment at end-IB to first event or time to last f/u for patients w/o 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 IA, relapse, second malignancy, or death as a first event; OS: from the time from study enroll. to death.
5.From enroll. to death.
6.From MRD assessment at end-IB to death.
8. EFS: from enroll. until the first occurrence of M3 marrow at the end of IA, relapse, second malignancy, or death as a first event); OS: from the time from study enroll to death from any cause.
Contact information
(Data source: WHO)
Universit? degli Studi Milano Bicocca ;Medical Reaserch Organisation
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)
Coordinamento Ricerca Clinica
Via Pergolesi, 33
Universit? degli Studi Milano Bicocca
dastoli.giuseppe@gmail.com
Contact for scientific information
(Data source: WHO)
Coordinamento Ricerca Clinica
Via Pergolesi, 33
Universit? degli Studi Milano Bicocca
dastoli.giuseppe@gmail.com
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)
EsPhALL2017COGAALL1631
2017-000705-20-AT
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