a study to investigate the sequencing strategy of pirtobrutinib after disease progression on first-line acalabrutinib treatment for adult participants with chronic lymphocytic leukemia or small lymphocytic lymphoma

Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Summary: to assess the efficacy and safety of pirtobrutinib in participants with cll/sll who have progressed on first-line treatment with acalabrutinib.

the purpose of this study is to assess the efficacy and safety of pirtobrutinib in participants with cll/sll who have progressed on first-line treatment with acalabrutinib. a subset of participants who have disease progression on pirtobrutinib will be retreated with acalabrutinib to assess whether relapsed cll can be re-sensitized to a covalent irreversible btk inhibitor such as acalabrutinib, and thereby, remain on treatment within the btk inhibitor class rather than transition into another cll/sll treatment. * the study duration for each participant will be up to 3 years in total. * for participants who receive pirtobrutinib alone, the visit frequency will be approximately every month for the first 6 months. after that, the visit frequency will be reduced to one visit approximately every 3 months for the subsequent 12 months. the final part of the treatment phase has 2 visits in the space of 6 months. there is one visit to the site after the treatment phase. * participants who have disease progression on pirtobrutinib and go on to receive acalabrutinib retreatment will visit the site approximately once every month for the first 6 months. after that, the visit frequency will be reduced to 2 visits in the space of 6 months. there is one visit to the site after the treatment phase.

Eligibility criteria:
inclusion criteria: * participant must be ≥ 18 at the time of signing the informed consent. * participants must have received acalabrutinib monotherapy as first-line treatment for cll/sll, have progressed per the iwcll criteria (hallek et al 2018) and be eligible for second-line treatment by the same criteria. * ecog performance status of 0, 1, or 2. * adequate organ and bm function. * adequate coagulation, defined as aptt or ptt and pt or inr not greater than 1.5 × uln. * participants have a clearly defined, documented and accessible start date of their first line acalabrutinib monotherapy for cll/sll. * participants are eligible for the acalabrutinib retreatment phase only if they have progressed on pirtobrutinib monotherapy per iwcll criteria. exclusion criteria: * major surgical procedure within 30 days before and not recovered adequately the first dose of study drug. * participants who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a btk inhibitor. * history of bleeding diathesis (eg, hemophilia, von willebrand disease). * history of stroke or intracranial hemorrhage within 6 months before first dose of study drug. * significant cardiovascular disease. * history of pml. * any active significant infection. * hiv positive * active hbv or hcv infection. * active cns involvement by lymphoma, leptomeningeal disease, or spinal cord compression. * active auto-immune cytopenia. * history of prior or current malignancy. * requires or receiving therapeutic anticoagulation with warfarin or equivalent vitamin k antagonists. * received a live virus vaccination within 28 days of first dose of study drug. * requires treatment with a strong cyp3a inhibitor or inducer. the use of strong cyp3a inhibitors within 1 week or strong cyp3a inducers within 3 weeks of the first dose of study drug is prohibited.

Keywords: chronic lymphocytic leukemia small lymphocytic lymphoma