{"entity":{"id":"amplify","kind":"trial","name":"AMPLIFY","aka":[],"tldr":"AMPLIFY is the trial behind the first all-oral, fixed-duration CLL regimen approved in the US (February 2026): 14 cycles of two pills, then stop.","summary":"AMPLIFY, trial NCT03836261 sponsored by AstraZeneca and published in the New England Journal of Medicine in 2025, is the trial behind the first all-oral, fixed-duration regimen approved for chronic lymphocytic leukaemia in the United States on 19 February 2026: fourteen cycles of acalabrutinib and venetoclax, then stop. It randomised 867 fit, previously untreated patients without del(17p) to acalabrutinib plus venetoclax, the same with obinutuzumab, or chemoimmunotherapy, met its primary progression-free survival endpoint for both experimental arms at three years, and showed a survival advantage for the doublet partly driven by COVID-19 deaths in the chemotherapy arm. Whether the triplet is worth its extra toxicity is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03836261","url":"https://clinicaltrials.gov/study/NCT03836261"},{"label":"FDA approval (19 Feb 2026)","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-venetoclax-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma"}],"tags":[],"related":[],"cancers":["cll","cll-treatment-naive"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["btk","bcl2","cd20"],"drugs":["acalabrutinib","venetoclax","obinutuzumab"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["ighv-status","del17p-tp53"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03836261","phase":"3","setting":"Fit, previously untreated CLL without del(17p)/TP53: fixed-duration acalabrutinib + venetoclax (AV) or + obinutuzumab (AVO) vs FCR/BR chemoimmunotherapy","sponsor":"AstraZeneca","result":"3-year PFS 76.5% (AV) / 83.1% (AVO) vs 66.5%.","started":"2019-02-25","startedType":"actual","yearReported":2024,"enrolled":867,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 3 years","primary":true,"unit":"%","arms":[{"name":"Acalabrutinib + venetoclax","n":291,"value":76.5},{"name":"Acalabrutinib + venetoclax + obinutuzumab","n":286,"value":83.1},{"name":"Chemoimmunotherapy (FCR/BR)","n":290,"value":66.5}],"source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-venetoclax-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma"},{"endpoint":"Progression-free survival (AV vs CIT)","arms":[{"name":"Acalabrutinib + venetoclax"},{"name":"Chemoimmunotherapy"}],"hr":0.65,"ci":[0.49,0.87],"source":"https://doi.org/10.1056/NEJMoa2409804"}],"replication":"GLOW and CAPTIVATE (ibrutinib-venetoclax), CLL13 (venetoclax-obinutuzumab ± ibrutinib), and SEQUOIA arm D (zanubrutinib-venetoclax) all show BTKi + BCL2i fixed-duration efficacy; the class effect is robust across three BTK inhibitors."},"route":"/trials/amplify/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"acalabrutinib","kind":"drug","name":"Acalabrutinib","route":"/drugs/acalabrutinib/"},{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"term":[{"id":"del17p-tp53","kind":"term","name":"del(17p) / TP53 aberration in CLL","route":"/terms/del17p-tp53/"},{"id":"ighv-status","kind":"term","name":"IGHV mutational status","route":"/terms/ighv-status/"}],"pairing":[{"id":"btki-plus-venetoclax-fixed-duration","kind":"pairing","name":"BTK inhibitor + venetoclax, fixed duration","route":"/pairings/btki-plus-venetoclax-fixed-duration/"}],"paper":[{"id":"paper-amplify-acalabrutinib-venetoclax-nejm-2025","kind":"paper","name":"AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients","route":"/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/"}]}}