Selumetinib in combination with dexamethasone for the treatment of relapsed/refractory RAS-pathway mutated paediatric and adult acute lymphoblastic leukaemia (SeluDex): study protocol for an international, parallel-group, dose-finding with expansion phase I/II trial.
adult oncology
clinical trials
leukaemia
paediatric oncology
Journal
BMJ open
ISSN: 2044-6055
Titre abrégé: BMJ Open
Pays: England
ID NLM: 101552874
Informations de publication
Date de publication:
04 Mar 2022
04 Mar 2022
Historique:
entrez:
5
3
2022
pubmed:
6
3
2022
medline:
28
4
2022
Statut:
epublish
Résumé
Event-free survival rates at 15 years for paediatric patients with relapsed/refractory acute lymphoblastic leukaemia (ALL) are 30%-50%, with 5-year survival for adult patients only 20%. Many patients with newly diagnosed and relapsed ALL harbour somatic RAS-signalling activation mutations. Induction therapy for ALL involves steroids, with preclinical data suggesting the combination of dexamethasone with the MEK1/2 inhibitor, selumetinib (ARRY-142886) has a synergistic anticancer effect. The SeluDex trial is an international, parallel-group, dose-finding with expansion, phase I/II trial to assess the selumetinib/dexamethasone combination in adult and paediatric patients with relapsed/refractory, RAS pathway mutant ALL. The Cancer Research UK Clinical Trials Unit at University of Birmingham is the UK Coordinating Centre, with national hubs in Copenhagen, Denmark; Monza, Italy; Münster, Germany; Paris, France; and Utrecht, Netherlands. Patients with morphologically proven relapsed/refractory or progressive B-cell precursor or T-cell ALL, with demonstrated RAS pathway activating mutations are eligible. Adult patients are Medical ethical committees of all the participating countries have approved the study protocol; initial (UK) ethics approval (17/YH/0123) was granted by Yorkshire & The Humber-Leeds West Research Ethics Committee. Participants are required to provide written informed consent/assent. Results will be disseminated through national and international presentations and peer-reviewed publications. ISRCTN92323261.
Identifiants
pubmed: 35246426
pii: bmjopen-2021-059872
doi: 10.1136/bmjopen-2021-059872
pmc: PMC8900053
doi:
Substances chimiques
AZD 6244
0
Benzimidazoles
0
Dexamethasone
7S5I7G3JQL
Banques de données
ISRCTN
['ISRCTN92323261']
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e059872Subventions
Organisme : Cancer Research UK
ID : C27943/A22304
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C27943/A23260
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C22436/A25354
Pays : United Kingdom
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: JI has received research funding from F. Hoffmann-La Roche.
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