NCT06812715

Clonal Dynamics of Chronic Lymphocytic Leukaemia Treated With Pirtobrutinib After Previous Treatment With Zanubrutinib

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Peter MacCallum Cancer Centre, Australia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Following confirmation of eligibility and registration to the study, patients will receive treatment with pirtobrutinib until progressive disease (PD) according to International Workshop on Chronic Lymphocytic Leukaemia (iwCLL) 2018 criteria, unacceptable toxicity, or patient withdrawal. Following first progression, treatment may continue if in the opinion of the investigator the patient is deriving clinical benefit. BTK mutational status and analysis of CLL clonal dynamics on peripheral blood will be performed prior to the first dose of treatment, Day 1 of each cycle thereafter while on study treatment, End of Treatment (EoT), and at time of PD. Response will be assessed by the investigator based on physical examination, CT scan (or MRI), haematology results, and bone marrow examinations according to iwCLL 2018 response criteria. Patients who discontinue treatment for any reason will have an EoT visit within 7 days after the last dose of treatment or decision to cease treatment. Additionally, they will have a Safety Follow-up visit 28 days + 7 days after the last dose of treatment or decision to discontinue treatment. Following these two visits, patients will move into the Follow-up Phase of the study where they will be assessed every 12 weeks ± 4 weeks. Patients with PD will be followed for survival and new anti-CLL therapy only. All patients will be followed up until the last registered patient has been on pirtobrutinib for 36 months without PD.

Conditions

• Chronic Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	Pirtobrutinib	Pirtobrutinib 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).

Timeline

• Start date: 2025-05-05
• Primary completion: 2029-05-01
• Completion: 2031-05-01
• First posted: 2025-02-06
• Last updated: 2025-08-06

Locations

3 sites across 1 country: Australia

Regulatory

• FDA-regulated drug study