{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:35:28Z","timestamp":1787016928831,"version":"build-2736575974"},"reference-count":30,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"unspecified","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C27943\/A22304"],"award-info":[{"award-number":["C27943\/A22304"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C27943\/A23260"],"award-info":[{"award-number":["C27943\/A23260"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,1,27]]},"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Event-free survival rates at 15 years for paediatric patients with relapsed\/refractory acute lymphoblastic leukaemia (ALL) are 30%\u201350%, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      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; M\u00fcnster, 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\n                      <jats:underline>&gt;<\/jats:underline>\n                      18 years old, ECOG\n                      <jats:underline>&lt;<\/jats:underline>\n                      2\u2009and paediatric &lt;18 years old, Lansky play scale \u226560%\u2009or Karnofsky score \u226560%. Phase I primary objective is the recommended phase II dose of selumetinib as defined by occurrence\/non-occurrence of dose limiting toxicities using the continual reassessment method; phase II will evaluate preliminary antileukaemic activity of the combination, as defined by morphological response 28 days post-treatment using a Bayesian approach. Target recruitment is between 26 and 42 patients (minimum 13 and maximum 21 per group), depending the number of phase I patients included in phase II.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Medical ethical committees of all the participating countries have approved the study protocol; initial (UK) ethics approval (17\/YH\/0123) was granted by Yorkshire &amp; The Humber\u2014Leeds 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"ISRCTN92323261\">ISRCTN92323261<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-059872","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T11:29:23Z","timestamp":1646393363000},"page":"e059872","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["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"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct03705507","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Tobias","family":"Menne","sequence":"first","affiliation":[{"name":"Northern Center for Cancer Care, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Slade","sequence":"additional","affiliation":[{"name":"Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomics Cancer, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-0245","authenticated-orcid":false,"given":"Joshua","family":"Savage","sequence":"additional","affiliation":[{"name":"Cancer Research UK Clinical Trials Unit, 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