{"entity":{"id":"aaml1031","kind":"trial","name":"AAML1031","aka":["COG AAML1031"],"tldr":"AAML1031 was the children's leukaemia trial that found adding bortezomib to standard chemotherapy did not help and caused more nerve damage, while a separate part of the trial suggested that adding the FLT3 blocker sorafenib does improve outcomes for children whose leukaemia carries a high load of the FLT3-ITD mutation.","summary":"AAML1031 was the Children's Oncology Group phase 3 trial for de novo acute myeloid leukaemia in patients under 30. Patients without a high allelic ratio FLT3-ITD mutation were randomised to standard chemotherapy (four courses, or three followed by allogeneic transplant for high-risk disease) with or without bortezomib on days 1, 4 and 8 of each course. Patients with high allelic ratio FLT3-ITD received sorafenib in three sequential cohorts that defined the dose and then added it to induction and as single-agent maintenance.\n\nBortezomib did not improve remission, event-free or overall survival and increased peripheral neuropathy and intensive care admissions. In the FLT3-ITD cohorts, patients given sorafenib had better event-free survival than a comparator group of high allelic ratio patients treated with identical chemotherapy without sorafenib, and multivariable analysis accounting for transplant and co-occurring favourable mutations confirmed the benefit. The trial is why the standard-of-care text for childhood acute myeloid leukaemia adds sorafenib to chemotherapy for high allelic ratio FLT3-ITD disease.","status":"mixed","asOf":"2026-09-22","links":[{"label":"ClinicalTrials.gov NCT01371981","url":"https://clinicaltrials.gov/study/NCT01371981"}],"tags":["soc-trials"],"related":[],"cancers":["aml-paediatric","aml-flt3","aml","leukaemia"],"sections":[],"technologies":["cytotoxic-chemotherapy","kinase-inhibitors"],"targets":[],"drugs":["bortezomib","sorafenib"],"companies":[],"institutions":["childrens-oncology-group"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-aaml1031-bortezomib-aplenc-haematologica-2020","paper-aaml1031-sorafenib-flt3-pollard-jco-2022"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01371981","phase":"3","setting":"Newly diagnosed acute myeloid leukaemia in patients under 30: standard chemotherapy with or without bortezomib (randomised), and for high allelic ratio FLT3-ITD disease the addition of sorafenib to chemotherapy and as maintenance (non-randomised cohorts)","sponsor":"National Cancer Institute (NCI)","result":"Bortezomib added to chemotherapy did not improve three-year event-free survival (44.8 percent against 47.0 percent) and added toxicity; sorafenib for high allelic ratio FLT3-ITD disease roughly halved the hazard of an event compared with matched patients treated without it.","yearReported":2020,"enrolled":1645,"enrolledBasis":"registry","outcomes":[{"endpoint":"Event-free survival at 3 years, bortezomib randomisation","primary":true,"unit":"%","arms":[{"name":"Chemotherapy + bortezomib","n":555,"value":44.8},{"name":"Chemotherapy alone","n":542,"value":47}],"p":"0.236","source":"https://doi.org/10.3324/haematol.2019.220962"},{"endpoint":"Overall survival at 3 years, bortezomib randomisation","unit":"%","arms":[{"name":"Chemotherapy + bortezomib","n":555,"value":63.6},{"name":"Chemotherapy alone","n":542,"value":67.2}],"p":"0.356","source":"https://doi.org/10.3324/haematol.2019.220962"},{"endpoint":"Complete remission after induction, bortezomib randomisation","unit":"%","arms":[{"name":"Chemotherapy + bortezomib","n":555,"value":89},{"name":"Chemotherapy alone","n":542,"value":91}],"p":"0.531","source":"https://doi.org/10.3324/haematol.2019.220962"},{"endpoint":"Event-free survival from study entry, high allelic ratio FLT3-ITD (hazard for patients not given sorafenib against sorafenib cohorts 2 and 3)","arms":[{"name":"Chemotherapy without sorafenib (comparator)","n":76},{"name":"Chemotherapy + sorafenib (cohorts 2 and 3)","n":72}],"hr":2.37,"ci":[1.45,3.88],"source":"https://doi.org/10.1200/jco.21.01612"},{"endpoint":"Relapse risk from complete remission, high allelic ratio FLT3-ITD (hazard for patients not given sorafenib)","arms":[{"name":"Chemotherapy without sorafenib (comparator)","n":76},{"name":"Chemotherapy + sorafenib (cohorts 2 and 3)","n":72}],"hr":3.03,"ci":[1.31,7.04],"p":"0.010","source":"https://doi.org/10.1200/jco.21.01612"}]},"route":"/trials/aaml1031/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"},{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","route":"/cancers/aml-flt3/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"sorafenib","kind":"drug","name":"Sorafenib","route":"/drugs/sorafenib/"}],"institution":[{"id":"childrens-oncology-group","kind":"institution","name":"Children's Oncology Group (COG)","route":"/institutions/childrens-oncology-group/"}],"paper":[{"id":"paper-aaml1031-bortezomib-aplenc-haematologica-2020","kind":"paper","name":"AAML1031: bortezomib with standard chemotherapy for children with acute myeloid leukaemia does not improve outcomes","route":"/key-papers/paper-aaml1031-bortezomib-aplenc-haematologica-2020/"},{"id":"paper-aaml1031-sorafenib-flt3-pollard-jco-2022","kind":"paper","name":"AAML1031: sorafenib combined with chemotherapy for children with high allelic ratio FLT3-ITD acute myeloid leukaemia","route":"/key-papers/paper-aaml1031-sorafenib-flt3-pollard-jco-2022/"}]}}