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NCT06839872 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: D8220R00065
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  ORR will be assessed after 12 cycles (each cycle lasts 28 days) of pirtobrutinib.

Secondary Outcomes (4)

• Investigator assessed ORR in participants with CLL/SLL.

  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 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 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 at every visit starting from acalabrutinib treatment through the study completion (for 3 years)

Study Arms (1)

Pirtobrutinib and Acalabrutinib

EXPERIMENTAL

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

Interventions

Pirtobrutinib DRUG

Patients will receive pirtobrutinib orally with dosing schedule as prescribed

Also known as: JAYPIRCA

Pirtobrutinib and Acalabrutinib

Acalabrutinib DRUG

Patients will receive acalabrutinib orally with dosing schedule as prescribed.

Also known as: CALQUENCE®

Pirtobrutinib and Acalabrutinib

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

pirtobrutinib; acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: February 21, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): July 28, 2028
• Study Completion (Estimated): July 29, 2030
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.