Actively Recruiting
Pirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi
Led by Kerry Rogers · Updated on 2026-02-19
30
Participants Needed
1
Research Sites
112 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Pirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) according to iwCLL 2018 guidelines
- Detectable CLL on blood or marrow flow cytometry at enrollment
- Age 18 years or older
- ECOG performance status between 0 and 2
- Currently taking and tolerating ibrutinib, acalabrutinib, or zanubrutinib for more than 4 weeks
- Evidence of progressive disease or doubling of absolute lymphocyte count in 6 months while on BTK inhibitor with ALC above 5 k/uL
- AST/ALT levels no more than 3 times the upper limit of normal or 5 times with liver involvement
- Bilirubin no more than 1.5 times the upper limit of normal or 3 times with liver involvement or Gilbert's disease
- Creatinine clearance of 30 or higher
- Absolute neutrophil count of 0.75 k/uL or higher without recent transfusion or growth factor, or any value if due to bone marrow involvement
- Hemoglobin 8 g/dL or higher without recent transfusion or growth factor, or any value if due to bone marrow involvement
- Platelets 50 k/uL or higher without recent transfusion or growth factor, or any value if due to bone marrow involvement
- Prothrombin and partial thromboplastin times no more than 1.5 times the upper limit of normal
- No known inherited qualitative platelet defects
- Willing and able to complete study activities and treatment
- Able to provide signed informed consent
- Willingness to use effective birth control during treatment and for specified times after last dose
- If retreated with pirtobrutinib, must have discontinued initial treatment within 12 months and meet criteria for progressive disease
You will not qualify if you...
- Inability to tolerate 2 liters of oral or IV hydration
- Prior venetoclax exposure over 13 months or known resistance to venetoclax
- Known allergy to pirtobrutinib or venetoclax ingredients
- Need for warfarin or vitamin K antagonist treatment during study
- History of bleeding disorders or major bleeding events with prior BTK inhibitor treatment
- History of stroke or brain hemorrhage within 6 months
- Unable to take oral medications
- Active malabsorption or conditions affecting drug absorption
- Current central nervous system involvement with CLL or SLL unless stable and approved by investigator
- Recent treatment with targeted, investigational, monoclonal antibody, or chemotherapy agents within specified timeframes
- Unresolved adverse events from prior treatment except alopecia or grade 2 neuropathy
- Recent stem cell transplant or CAR-T therapy with ongoing complications
- Active second cancer unless in remission with life expectancy over 2 years
- Psychiatric or social conditions limiting study compliance
- Active uncontrolled autoimmune blood disorders with recent therapy changes
- Uncontrolled infections or clinically significant active diseases
- Significant cardiovascular diseases or arrhythmias
- Prolonged QT interval beyond 470 msec
- Active hepatitis B or C infection or positive viral markers without clearance
- Known HIV infection or positive HIV test at screening
- Active cytomegalovirus infection
- Recent treatment with strong CYP3A or P-gp inhibitors or inducers
- Pregnancy, breastfeeding, or planning to breastfeed during study and specified times after
- Major surgery within 4 weeks prior to screening
- Live vaccine within 28 days of screening
- Currently incarcerated
- History of progressive multifocal leukoencephalopathy (PML) or JC virus infection
- History of seizure disorder unless controlled without seizures for 1 year
- For pirtobrutinib retreatment, no new medical conditions that would affect safety
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Actively Recruiting
Research Team
T
The Ohio State University Comprehensive Cancer Center
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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