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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.

Base di dati: BASEC (Importata da 26.07.2024), WHO (Importata da 27.07.2024)
Cambiato: 16 lug 2024, 12:34
Categoria di malattie: Leucemia

Descrizione riassuntiva della sperimentazione (Fonte di dati: 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.

Malattie studiate(Fonte di dati: BASEC)

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

Health conditions (Fonte di dati: WHO)

Philadelphia positive Acute Lymphoblastic 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]

Malattia rara (Fonte di dati: BASEC)

No

Interventi esaminati (p. es. medicamento, terapia, campagna) (Fonte di dati: 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 (Fonte di dati: 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:
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

Pharmaceutical Form: Tablet
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Other descriptive name: METHOTREXATE

Pharmaceutical Form:
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4
Other descriptive name: CYTARABINE

Pharmaceutical Form:
INN or Proposed INN: ETOPOSIDE
CAS Number: 33419-42-0
Other descriptive name: ETOPOSIDE

Pharmaceutical Form:
INN or Proposed INN: VINCRISTINE
CAS Number: 57-22-7

Pharmaceutical Form:
INN or Proposed INN: IFOSFAMIDE
CAS Number: 3778-73-2

Pharmaceutical Form:
INN or Proposed

Criteri per la partecipazione alla sperimentazione (Fonte di dati: BASEC)

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

Criteri di esclusione (Fonte di dati: BASEC)

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

Inclusion/Exclusion Criteria (Fonte di dati: 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.a. 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.
b. B-ALL 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.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.

Altri dati sulla sperimentazione nel registro primario dell’OMS

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000705-20

Altri dati sulla sperimentazione dalla banca dati dell’OMS (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2017-000705-20
Altre informazioni sulla sperimentazione

Data di registrazione della sperimentazione

16 ago 2018

Inserimento del primo partecipante

5 nov 2018

Stato di reclutamento

Authorised-recruitment may be ongoing or finished

Titolo scientifico (Fonte di dati: 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

Tipo di sperimentazione (Fonte di dati: WHO)

Interventional clinical trial of medicinal product

Disegno della sperimentazione (Fonte di dati: 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

Fase (Fonte di dati: WHO)

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

Punti finali primari (Fonte di dati: WHO)

Main Objective: To compare disease-free survival (DFS) of Standard Risk (SR) Ph+ ALL patients treated with continuous imatinib combined with either the EsPhALL chemotherapy backbone (Arm A) or a less intensive a high-risk COG ALL chemotherapy backbone (Arm B), according to the randomization result. A non-inferiority design will be applied in order to evaluate whether there is significant erosion in DFS in SR patients treated with the less intensive Arm B compared with Arm A.;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 participants.
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): 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.

Punti finali secondari (Fonte di dati: WHO)

Secondary end point(s): 1.1. 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.

Contatto per informazioni (Fonte di dati: WHO)

Universit? degli Studi Milano Bicocca

Risultati della sperimentazione (Fonte di dati: WHO)

Sintesi dei risultati

ancora nessuna informazione disponibile

Collegamento ai risultati nel registro primario

ancora nessuna informazione disponibile

Informazioni sulla disponibilità dei dati dei singoli partecipanti

ancora nessuna informazione disponibile

Siti di esecuzione della sperimentazione

Siti di esecuzione in Svizzera (Fonte di dati: BASEC)

Aarau, Basilea, Bellinzona, Berna, Ginevra, Losanna, Luzern, San Gallo, Zurigo

Paesi di esecuzione (Fonte di dati: 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

Contatto per maggiori informazioni sulla sperimentazione

Dati della persona di contatto in Svizzera (Fonte di dati: BASEC)

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

Contatto per informazioni generali (Fonte di dati: WHO)

Coordinamento Ricerca Clinica
Via Pergolesi, 33
Universit? degli Studi Milano Bicocca
dastoli.giuseppe@gmail.com

Contatto per informazioni scientifiche (Fonte di dati: WHO)

Coordinamento Ricerca Clinica
Via Pergolesi, 33
Universit? degli Studi Milano Bicocca
dastoli.giuseppe@gmail.com

Autorizzazione da parte della commissione d’etica (Fonte di dati: BASEC)

Nome della commissione d’etica che rilascia l’autorizzazione (nel caso di studi multicentrici solo la commissione direttiva)

Kantonale Ethikkommission Zürich

Data di autorizzazione da parte della commissione d’etica

20.08.2019

Altri numeri di identificazione delle sperimentazioni

Numero di identificazione della sperimentazione della commissione d’etica (BASEC-ID) (Fonte di dati: BASEC)

2019-01172

Secondary ID (Fonte di dati: WHO)

EsPhALL2017/COGAALL1631
2017-000705-20-AT
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