Phase 2 Study of Combination Pirtobrutinib (LOXO-305) and Venetoclax in CLL Patients With Resistance to Covalent BTKi
Kerry Rogers
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.
Description
PRIMARY OBJECTIVE: I. Determine if combination pirtobrutinib and venetoclax can induce undetectable minimal residual disease (uMRD) in CLL patients with resistance to ibrutinib, acalabrutinib, or zanubrutinib. OUTLINE: Patients receive pirtobrutinib orally (PO) once daily (QD) on days 1-28 of each cycle and receive venetoclax PO QD on days 1-28 of cycles 2-20. Cycles repeat every 28 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression within 12 months of stopping combination treatment may receive pirtobrutinib P…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Diagnosis of CLL or SLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines * Detectable CLL on flow cytometry of the blood or marrow at time of enrollment * Age ≥ 18 years old * Eastern Cooperative Oncology Group (ECOG) performance 0-2 * Currently taking ibrutinib, acalabrutinib, or zanubrutinib at any daily dose and tolerating it for \> 4 weeks * Evidence of progressive disease by iwCLL 2018 criteria for progressive disease or doubling of absolute lymphocyte count (ALC) in ≤ 6 months while on BTK inhibitor provided ALC is \>…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration and biopsy
- ProcedureBone Marrow Biopsy
Undergo bone marrow aspiration and biopsy
- ProcedureComputed Tomography
Undergo CT
- DrugPirtobrutinib
Given PO
- DrugVenetoclax
Given PO
Location
- Ohio State University Comprehensive Cancer CenterColumbus, Ohio