This is a multicentre single-arm prospective phase II trial evaluating pirtobrutinib in the treatment of relapsed/refractory (R/R) Chronic Lymphocytic Leukaemia (CLL) patients who have previously received zanubrutinib, and to specifically evaluate Bruton Tyrosine Kinase (BTK) mutational status (clonal dynamics) before, during and after treatment with pirtobrutinib.
Patient has provided written informed consent using the PIPOZA Patient Information and Consent Form (PICF)
Confirmed diagnosis of CLL according to iwCLL 2018 criteria, also including CLL with atypical immunophenotype
Prior systemic therapy, which must include zanubrutinib as the most recent prior line of therapy. Patients must have received at least one cycle (28 days) of zanubrutinib
Where the original indication for treatment has not resolved with initial therapy and it is considered reasonable to initiate second-line treatment without waiting for formal disease progression to be manifest
Known or suspected Richter's Transformation to diffuse large B-cell lymphoma, prolymphocytic leukaemia, or Hodgkin lymphoma at any time prior to registration
Known or suspected history of central nervous system involvement
Active graft versus host disease
Cytopenias from incomplete blood cell count recovery post-transplant or CAR-T therapy
Single group
Pirtobrutinib
DrugPirtobrutinib is a first-in-class, oral noncovalent Bruton tyrosine kinase (BTK) inhibitor (BTKi) that was approved in January 2023 in the United States for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) and later that same year CLL. It is currently being investigated across several global randomised phase III trials for frontline and R/R chronic lymphocytic leukaemia (CLL).
Cloncal dynamics of BTK mutations in CLL before, during and after treatment with pirtobrutinib
Overall response rate in CLL with pirtobrutinib after prior immediate zanubrutinib
The efficacy as assessed by time to response (TTR)
The time from the start of pirtobrutinib to the first objective response observed for patients who achieves a complete remission (CR), complete remission with an incomplete marrow recovery (CRi), nodular partial remission (nPR), partial remission (PR) or the initiation of subsequent anticancer therapy. TTR also includes partial remission with lymphocytosis (PR-L) as sensitivity analysis
Efficacy as assessed by Duration of Response (DOR)
The time from onset of a CR, CRi, nPR, PR to the earlier of the documentation of definitive progressive disease (\[PD\] per iwCLL 2018 criteria) or death from any cause, whichever occurred first. Duration of response and time to response will be evaluated for responders (CR, CRi, nPR, PR) only. DOR including PR-L as a response will be analysed with the same method as DOR
Efficacy as assessed by Disease Control Rate (DCR)
The percentage of patients who have achieve CR, CRi, nPR, PR, PR-L, or SD
Additional elements of clonal dynamics in CLL
Additional genomic profiling and analyses
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Peter MacCallum Cancer Centre, Australia
Lead sponsor
Eli Lilly and Company
Collaborator
