Loxo III: Trial of Fixed Pirtobrutinib + Vene and Rituximab in CLL/SLL (Leukemia)

We are doing this study to find out if an investigational drug called pirtobrutinib (LOXO-305) is a safe and effective treatment for CLL/SLL when it is given in combination with venetoclax and rituximab. The combination of venetoclax and rituximab is an approved therapy that is safe and effective for some people who did not respond to a first line of treatment or had their cancer progress after treatment. We want to know if adding LOXO-305 to the approved therapy will have better results.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Adults ages 18+ who:

• Are diagnosed with CLL/SLL
• Have received one previous line of treatment that may include a BTK inhibitor
• Did not respond to treatment; OR
• Responded to treatment at first but their CLL/SLL later progressed; OR
• Had to stop treatment for CLL/SLL because of side effects

For more information about who can join this study, contact the study team at terri.lucas@duke.edu.

There are 3 parts to this study: a screening period, a dosing period, and a follow-up period.

If you choose to join this study, during the screening period you will:

• Have physical exams
• Have blood draws and give urine samples
• Answer questionnaires
• Have imaging scans (CT or MRI)
• Have a biopsy of your lymph node(s), if necessary
• Have heart scans (electrocardiogram)

If you are found to be eligible during screening, you will proceed to the dosing period. During this period, you will:

• Be randomly assigned (like a coin flip) to 1 of 2 study arms
• Participants assigned to Arm A will take LOXO-305 along with venetoclax and rituximab
• Participants assigned Arm B will take only venetoclax and rituximab

LOXO-305 and venetoclax are tablets that are taken by mouth every day. Rituximab is an infusion that you will get by IV in our clinic approximately 1 time per month. The dosing period in this study will last for up to 28 months.

The follow-up period begins when you finish the dosing period. During this period, you will:

• Visit our clinic for follow-up visits every 3 months for the first 2 years after dosing ends
• Visit our clinic every 6 months after the first 2 years of follow-up
• Have physical exams
• Have blood draws
• Have imaging scans and heart scans
• Have a bone marrow biopsy (optional)