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

Status: withdrawn

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

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.

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.

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.

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