BRUIN CLL-322: A Phase 3 Open-Label, Randomized Study of Fixed-Duration Pirtobrutinib Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Trial in Progress)

William G. Wierda, John M. Pagel, Mathew S. Davids, Pier Luigi Zinzani, Yi Lu, Hui Liu, Safi Shahda, Ching Ching Leow, Constantine S. Tam, Jennifer Woyach, Toby A. Eyre, Anthony R. Mato

Research output: Contribution to journalMeeting Abstractpeer-review


Context: Currently, the majority of patients with chronic lymphocytic leukemia (CLL) who require treatment receive a covalent Bruton's tyrosine kinase inhibitor (BTKi) as their first standard of care targeted therapy. The MURANO study established the time-limited combination of venetoclax plus rituximab (2 years) as a standard of care regimen for patients with relapsed/refractory (R/R) CLL or small lymphocytic lymphoma (SLL). MURANO enrolled very few patients who were previously treated with a covalent BTKi. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that inhibits both wild-type and C481-mutated BTK with equally low nM potency. Objective: Adding fixed-duration pirtobrutinib to the MURANO regimen may allow for deeper remissions and longer disease control and generate a clinically relevant dataset in a population of patients with BTKi-pretreated R/R CLL/SLL. Design: BRUIN CLL-322 is a randomized, open-label, global phase 3 trial comparing fixed duration pirtobrutinib plus venetoclax and rituximab with standard venetoclax and rituximab in patients with R/R CLL/SLL. Approximately 600 patients will be randomized 1:1. Randomization will be stratified by 17p deletion (yes/no) and prior BTKi experience (discontinuation due to progressive disease vs. due to other reasons vs. no prior BTKi exposure). Setting: Global; community hospitals, academic medical centers. Patients: Eligible patients are adults with a diagnosis of CLL/SLL who require therapy per iwCLL 2018 criteria and who received prior therapy that may or may not include a covalent BTKi. Key exclusion criteria include CNS involvement by CLL/SLL, Richter transformation at any time pre-enrollment, history of allogeneic or autologous stem cell transplant or chimeric antigen receptor (CAR) T-cell therapy within 60 days, and prior therapy with a BCL2 inhibitor or non-covalent BTKi. There will be no exclusion based on the number of lines of prior therapy. Intervention: Fixed-duration pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab. Main Outcome Measures: The primary endpoint is progression-free survival per iwCLL criteria assessed by an independent review committee. Secondary endpoints include overall response rate, overall survival, time to next treatment, event-free survival, safety and tolerability, and patient-reported outcomes. This global study is currently enrolling patients (NCT04965493). Results: This study is a trial in progress. Conclusions: This study is a trial in progress.

Original languageEnglish
Article numberCLL-116
Pages (from-to)S267
Number of pages1
JournalClinical Lymphoma, Myeloma and Leukemia
Publication statusPublished - Oct 2022
Externally publishedYes
EventSociety of Hematologic Oncology Annual Meeting 2022 - Houston, United States of America
Duration: 28 Sept 20221 Oct 2022
Conference number: 10th


  • BCL2i
  • BTKi
  • chronic lymphocytic leukemia
  • CLL
  • pirtobrutinib
  • Trial-in-Progress
  • venetoclax

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