Pirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi
NCT Number: NCT06466122
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|PROCEDURE: Computed Tomography|DRUG: Pirtobrutinib|DRUG: Venetoclax
Sponsor: Kerry Rogers
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-31
Completion Date: 2025-12-31
Locations: Ohio State University Comprehensive Cancer Center, Columbus, Ohio, 43210, United States

Summary:
This phase II trial tests how well pirtobrutinib (LOXO-305) and venetoclax works in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that remains despite treatment (resistant) with covalent bruton tyrosine kinase inhibitors (BTKi). Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the a protein that signals cancer cells to multiply. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving pirtobrutinib and venetoclax may kill more cancer cells in patients with CLL or SLL that is resistant to covalent BTKi.

Primary Outcome Measures: Rate of undetectable minimal residual disease (uMRD), The rate of uMRD will be defined as the percentage of patients who have uMRD in both the peripheral blood and bone marrow at C21D1., At cycle 21 day 1 (C21D1) [each cycle lasts 28 days]
Secondary Outcome Measures: Best overall response rate (ORR), Best ORR will be estimated with exact 95% confidence intervals., At cycle 21 day 1 (C21D1) [each cycle lasts 28 days]|Overall Response Rate (ORR), ORR will be estimated with exact 95% confidence intervals., At cycle 21 day 1 (C21D1) [each cycle lasts 28 days]|Progression-free survival (PFS) for all patients, Clinical disease progression will be assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria. PFS will be described using the method of Kaplan-Meier. Median and/or estimates at clinically meaningful time points for PFS will be reported with 95% confidence intervals., At start of treatment to progression or death up to 18 months after completion of study treatment|PFS in patients who achieve uMRD and those who do not achieve uMRD with pirtobrutinib and venetoclax, Clinical disease progression will be assessed by iwCLL 2018 criteria. PFS will be described using the method of Kaplan-Meier. Median and/or estimates at clinically meaningful time points for PFS will be reported with 95% confidence intervals., At end of treatment to progression or death up to 18 months after completion of study treatment|Overall survival (OS) for all patients, OS will be described using the method of Kaplan-Meier. Median and/or estimates at clinically meaningful time points for OS will be reported with 95% confidence intervals., At start of treatment to death up to 18 months after completion of study treatment|OS for patients who achieve uMRD and those who do not achieve uMRD with pirtobrutinib and venetoclax, OS will be described using the method of Kaplan-Meier. Median and/or estimates at clinically meaningful time points for OS will be reported with 95% confidence intervals., At end of treatment to death up to 18 months after completion of study treatment|Incidence of adverse events (AEs), AEs will be summarized by type, severity and perceived attribution according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Hematologic AEs will be graded according to CLL specific criteria described in the iwCLL 2018 guidelines. The maximum grade for each type of AE will be recorded for each patient, and at a minimum, frequency tables will be reviewed to determine AE patterns. The number of patients who discontinue treatment due to AE will be summarized., Up to 28 days after last dose of study drugs