Ascend: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia: Journal of Clinical Oncology

P. Ghia, A. Pluta, M. Wach, D. Lysak, T. Kozak, M. Simkovic, P. Kaplan, I. Kraychok, A. Illes, J. de la Serna, S. Dolan, P. Campbell, G. Musuraca, A. Jacob, E. Avery, J.H. Lee, W. Liang, P. Patel, C. Quah, W. Jurczak

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE Acalabrutinib, a highly selective, potent, Bruton tyrosine kinase inhibitor, was evaluated in this global, multicenter, randomized, open-label, phase III study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). METHODS Eligible patients, aged $ 18 years with R/R CLL, were randomly assigned 1:1 centrally and stratified by del(17p) status, Eastern Cooperative Oncology Group performance status score, and number of prior lines of therapy. Patients received acalabrutinib monotherapy or investigator’s choice (idelalisib plus rituximab [I-R] or bendamustine plus rituximab [B-R]). The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC) in the intent-to-treat population. Key secondary end points included IRC-assessed overall response rate, overall survival, and safety. RESULTS From February 21, 2017, to January 17, 2018, a total of 398 patients were assessed for eligibility; 310 patients were randomly assigned to acalabrutinib monotherapy (n 5 155) or investigator’s choice (n 5 155; I-R, n 5 119; B-R, n 5 36). Patients had received a median of two prior therapies (range, 1-10). After a median follow-up of 16.1 months (range, 0.03-22.4 months), median PFS was significantly longer with acalabrutinib monotherapy (PFS not reached) compared with investigator’s choice (16.5 months [95% CI, 14.0 to 17.1 months]; hazard ratio, 0.31 [95% CI, 0.20 to 0.49]; P, .0001). Estimated 12-month PFS was 88% (95% CI, 81% to 92%) for acalabrutinib and 68% (95% CI, 59% to 75%) for investigator’s choice. Serious adverse events occurred in 29% of patients (n 5 44 of 154) treated with acalabrutinib monotherapy, 56% (n 5 66 of 118) with I-R, and 26% (n 5 9 of 35) with B-R. Deaths occurred in 10% (n 5 15 of 154), 11% (n 5 13 of 118), and 14% (n 5 5 of 35) of patients receiving acalabrutinib monotherapy, I-R, and B-R, respectively. CONCLUSION Acalabrutinib significantly improved PFS compared with I-R or B-R and has an acceptable safety profile in patients with R/R CLL. © 2020 by American Society of Clinical Oncology.
Original languageEnglish
Pages (from-to)2849-2861
Number of pages13
JournalJ. Clin. Oncol.
Volume38
Issue number25
DOIs
Publication statusPublished - 2020

Keywords

  • acalabrutinib
  • alanine aminotransferase
  • aspartate aminotransferase
  • bendamustine
  • hemoglobin
  • idelalisib
  • rituximab
  • adult
  • aged
  • alanine aminotransferase blood level
  • allergic bronchopulmonary aspergillosis
  • anemia
  • atrial fibrillation
  • brain hemorrhage
  • cancer combination chemotherapy
  • cancer patient
  • cancer survival
  • chronic lymphatic leukemia
  • colitis
  • Conference Paper
  • constipation
  • controlled study
  • contusion
  • coughing
  • death
  • diarrhea
  • drug dose reduction
  • drug efficacy
  • drug safety
  • drug withdrawal
  • fatigue
  • female
  • fever
  • follow up
  • gastrointestinal hemorrhage
  • headache
  • hematoma
  • hematuria
  • hemoglobin blood level
  • human
  • hypertension
  • infusion related reaction
  • leukemia relapse
  • lung mycosis
  • major clinical study
  • male
  • monotherapy
  • multicenter study
  • multiple cycle treatment
  • nausea
  • neutropenia
  • neutrophil count
  • non melanoma skin cancer
  • overall response rate
  • overall survival
  • phase 3 clinical trial
  • platelet count
  • pneumonia
  • priority journal
  • progression free survival
  • randomized controlled trial
  • rash
  • respiratory tract infection
  • second cancer
  • side effect
  • Streptococcus pneumonia
  • thrombocytopenia
  • treatment duration
  • tumor bleeding
  • upper respiratory tract infection

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