A Phase 2 interventional study of Pirtobrutinib and Acalabrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, sponsored by AstraZeneca. Withdrawn. Open to participants aged 18 Years to 110 Years. Per ClinicalTrials.gov, last updated 2025-06-05.
Sponsored by AstraZeneca · Phase 2, Interventional, and Treatment
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.
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Exclusion Criteria:
Participants will receive dose A of pirtobrutinib starting Cycle 1 Day 1 for up to 24 cycles or until disease progression, unacceptable toxicity, death, or withdrawal of consent. If they progress on pirtobrutinib, a subset will receive dose B of acalabrutinib starting Cycle 1 Day 1 for up to 12 cycles or until disease progression, death, intolerance, unacceptable toxicity, or withdrawal of consent. Those benefiting from treatment will enter the Disease Follow-up period, continuing with pirtobrutinib or acalabrutinib until disease progression, unacceptable toxicity, death, or withdrawal of consent. After 36 months from starting pirtobrutinib, participants can continue receiving treatment off-trial if beneficial, in consultation with their physician.
Drug: Pirtobrutinib · Drug: Acalabrutinib
Patients will receive pirtobrutinib orally with dosing schedule as prescribed
Also known as: JAYPIRCA
Patients will receive acalabrutinib orally with dosing schedule as prescribed.
Also known as: CALQUENCE®
Objective Response Rate (ORR) in participants with CLL/SLL.
ORR is defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per the iwCLL Criteria as assessed by the investigator.
Time frame: ORR will be assessed after 12 cycles (each cycle lasts 28 days) of pirtobrutinib.
Investigator assessed ORR in participants with CLL/SLL.
ORR is defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per the iwCLL Criteria as assessed by the investigator.
Time frame: ORR will be assessed after 24 cycles (each cycle is 28 days) of pirtobrutinib and at 3 years from Cycle 1: Day 1 of pirtobrutinib.
Progression free Survival (PFS) in participants with CLL/SLL.
PFS is defined as time from date of the first dose of pirtobrutinib until disease progression per the iwCLL Criteria as assessed by the investigator, or death due to any cause in the absence of disease progression.
Time frame: PFS will be assessed at 24 months of pirtobrutinib treatment.
Safety and tolerability of pirtobrutinib in CLL/SLL following disease progression on first-line acalabrutinib in participants with CLL/SLL.
Safety and tolerability will be evaluated as the number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs), and AE leading to treatment discontinuation.
Time frame: Safety and tolerability will be evaluated at every visit starting from pirtobrutinib treatment through the study completion (for 3 years)
Safety of acalabrutinib retreatment following disease progression on pirtobrutinib in participants with CLL/SLL.
Safety will be evaluated as the number of participants with Adverse Events (AEs), Serious Adverse Events (SAEs), and AE leading to treatment discontinuation.
Time frame: Safety will be evaluated at every visit starting from acalabrutinib treatment through the study completion (for 3 years)
No study locations are listed for this record.
Plan to share: Yes — Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting information: Study protocol, Sap
No publications or documents are linked to this record.
This study is withdrawn, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.
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