{"entity":{"id":"paper-acalabrutinib-cll-n-engl-j-med-2016","kind":"paper","name":"Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia","aka":[],"tldr":"Phase 2 or 3 results paper on Acalabrutinib in Chronic lymphocytic leukaemia, in New England Journal of Medicine (2016), one of the most cited Europe PMC records with Acalabrutinib in its title.","summary":"Background: Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.\n\nMethods: In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion.\n\nResults: The median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis; the remaining 5% of patients had stable disease. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter's transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred.\n\nConclusions: In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. (Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443.).\n\nIndexed on Europe PMC as PubMed record 26641137 (DOI 10.1056/nejmoa1509981). Its title names Acalabrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Clinical Trial, Phase I, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"BTK degraders to pre-empt resistance in frontline CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2016","url":"https://doi.org/10.1056/nejmoa1509981"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26641137/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26641137"},{"label":"ClinicalTrials.gov NCT02029443","url":"https://clinicaltrials.gov/study/NCT02029443"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct02029443"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/nejmoa1509981","pmid":"26641137","authors":"Byrd JC, Harrington B, O'Brien S, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Acalabrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Acalabrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-acalabrutinib-cll-n-engl-j-med-2016/","neighbours":{"trial":[{"id":"nct02029443","kind":"trial","name":"ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia","route":"/trials/nct02029443/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-btk-degrader-frontline","kind":"idea","name":"BTK degraders to pre-empt resistance in frontline CLL","route":"/ideas/idea-btk-degrader-frontline/"}]}}