{"entity":{"id":"ratify","kind":"trial","name":"RATIFY (CALGB 10603)","aka":[],"tldr":"The trial that made FLT3 the first targetable mutation in AML: adding midostaurin to chemotherapy tripled median survival.","summary":"3,277 patients screened to randomise 717 with FLT3-ITD or TKD mutations. Median OS 74.7 vs 25.6 months (HR 0.78, 95% CI 0.63-0.96, p=0.009); 4-year OS 51.4% vs 44.3%; benefit across ITD allelic ratio and TKD subgroups and irrespective of transplant. NEJM 2017. Established the template of TKI added to intensive induction that QuANTUM-First later refined.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00651261","url":"https://clinicaltrials.gov/study/NCT00651261"},{"label":"NEJM 2017","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1614359"}],"tags":[],"related":[],"cancers":["aml","aml-flt3"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["flt3"],"drugs":["midostaurin","cytarabine-7-3"],"companies":["alliance-oncology","novartis"],"institutions":[],"pathways":[],"terms":["flt3-itd-allelic-ratio","eln-risk"],"trials":[],"people":["richard-stone"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00651261","phase":"3","setting":"Newly diagnosed FLT3-mutated AML, age 18-59: midostaurin vs placebo added to 7+3, consolidation, and one year of maintenance","sponsor":"Alliance / Novartis","result":"Median OS 74.7 vs 25.6 months; HR 0.78.","started":"2008-04","startedType":"actual","yearReported":2017,"enrolled":717,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival (median)","primary":true,"unit":"months","arms":[{"name":"Midostaurin + 7+3","n":360,"value":74.7},{"name":"Placebo + 7+3","n":357,"value":25.6}],"hr":0.78,"ci":[0.63,0.96],"p":"0.009","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1614359"},{"endpoint":"4-year overall survival","unit":"%","arms":[{"name":"Midostaurin","value":51.4},{"name":"Placebo","value":44.3}],"source":"https://doi.org/10.1056/NEJMoa1614359"}],"replication":"QuANTUM-First (quizartinib) independently confirmed that FLT3 inhibition added to 7+3 improves OS in FLT3-ITD AML; real-world registries reproduce the RATIFY benefit in patients up to age 70."},"route":"/trials/ratify/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-flt3","kind":"cancer","name":"FLT3-mutated acute myeloid leukaemia","route":"/cancers/aml-flt3/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"flt3","kind":"target","name":"FLT3","route":"/targets/flt3/"}],"drug":[{"id":"cytarabine-7-3","kind":"drug","name":"Cytarabine + anthracycline ('7+3')","route":"/drugs/cytarabine-7-3/"},{"id":"midostaurin","kind":"drug","name":"Midostaurin","route":"/drugs/midostaurin/"}],"company":[{"id":"alliance-oncology","kind":"company","name":"Alliance for Clinical Trials in Oncology","route":"/companies/alliance-oncology/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"eln-risk","kind":"term","name":"ELN 2022 risk classification","route":"/terms/eln-risk/"},{"id":"flt3-itd-allelic-ratio","kind":"term","name":"FLT3-ITD allelic ratio","route":"/terms/flt3-itd-allelic-ratio/"}],"person":[{"id":"richard-stone","kind":"person","name":"Richard M. Stone","route":"/people/richard-stone/"}],"pairing":[{"id":"flt3i-plus-7-3","kind":"pairing","name":"FLT3 inhibitor + intensive chemotherapy","route":"/pairings/flt3i-plus-7-3/"}],"paper":[{"id":"paper-ratify-midostaurin-nejm-2017","kind":"paper","name":"RATIFY: midostaurin added to chemotherapy for acute myeloid leukaemia with a FLT3 mutation","route":"/key-papers/paper-ratify-midostaurin-nejm-2017/"}]}}