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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
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

NCT06839872

WithdrawnPhase 2

Sponsor: AstraZeneca

Conditions: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Interventions: Pirtobrutinib, Acalabrutinib

To assess the efficacy and safety of pirtobrutinib in participants with CLL/SLL who have progressed on first-line treatment with acalabrutinib.

Eligibility overview

Sex: ALL

Age: 18 Years to 110 Years

Healthy volunteers: No

Study type: INTERVENTIONAL

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.