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Study of Pirtobrutinib, Venetoclax and Rituximab combination compared to Venetoclax and Rituximab in previously treated Chronic Lymphocytic Leukemia patients

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on treating patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, which are types of blood cancers affecting white blood cells. The study will test a combination of three medications: pirtobrutinib, venetoclax, and rituximab. The purpose is to determine if adding pirtobrutinib to the combination of venetoclax and rituximab improves outcomes for patients who have already received previous treatment for their disease.

The medications will be given in different ways: pirtobrutinib and venetoclax are taken as tablets by mouth, while rituximab is given through an intravenous infusion (through a vein). The study compares two groups of patients - one group receives all three medications (pirtobrutinib, venetoclax, and rituximab), while the other group receives only venetoclax and rituximab.

During the study, patients will receive treatment for up to two years. Throughout this time, doctors will monitor how well the treatment is working and track any changes in the disease. The main focus will be on how long patients remain without their disease getting worse after starting treatment.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial evaluation

    You will undergo an evaluation to confirm your chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) diagnosis.

    Medical tests will be performed to check your blood counts, including platelets, hemoglobin, and neutrophil count.

    Your kidney function and overall physical condition will be assessed using the ECOG Performance Status scale.

  2. Step 2

    Treatment assignment

    You will be randomly assigned to one of two treatment groups:

    Group 1: Pirtobrutinib (taken by mouth) plus venetoclax (taken by mouth) and rituximab (given through a vein)

    Group 2: Venetoclax (taken by mouth) and rituximab (given through a vein)

  3. Step 3

    Treatment period

    Your treatment will follow a fixed-duration schedule.

    You will take oral medications daily according to your assigned treatment group.

    Rituximab will be administered through an intravenous infusion according to a predetermined schedule.

    Regular assessments will monitor your response to treatment and any side effects.

  4. Step 4

    Follow-up period

    After completing treatment, you will continue to be monitored to assess how well the therapy worked.

    Regular check-ups will track your disease status and overall health.

    The study will continue until 2027.

Who can join the trial?

7 criteria

  • Must be 18 years or older to participate
  • Must have a confirmed diagnosis of CLL/SLL (Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma) that requires treatment according to current medical guidelines
  • Must have received at least one previous treatment, which may include a specific type of therapy called BTK inhibitor (a medication that blocks certain proteins involved in cancer growth)
  • Must have adequate blood counts: - Platelets: at least 50,000 per microliter - Hemoglobin: at least 8 grams per deciliter - Neutrophils (white blood cells that fight infection): at least 1,000 per microliter
  • Must have proper functioning organs
  • Must have an ECOG Performance Status of 0-2 (a scale that measures a person's ability to perform daily activities and self-care, where 0 means fully active and 2 means able to do light activities but resting less than half the day)
  • Must have kidney function showing creatinine clearance of at least 30 milliliters per minute (a measure of how well your kidneys are filtering waste from your blood)

Who cannot join the trial?

14 criteria

  • Prior treatment with BTK inhibitors (medications that block an enzyme called Bruton's tyrosine kinase)
  • Active or uncontrolled autoimmune disease requiring systemic treatment (conditions where the immune system attacks healthy cells)
  • Known active central nervous system lymphoma (cancer in the brain or spinal cord)
  • History of other cancers within 2 years before starting the study, except for successfully treated skin cancers or early-stage cancers
  • Significant heart problems including:
    • Uncontrolled irregular heartbeat
    • Heart failure with reduced heart function
    • Recent heart attack
    • Active, uncontrolled infections requiring treatment
    • Known hepatitis B or C infection or HIV positive status
    • Major surgery within 4 weeks before starting the study
    • Pregnancy or breastfeeding
    • Mental conditions that could interfere with study participation
    • Use of medications that strongly affect certain liver enzymes (CYP3A inhibitors or inducers)
    • Any condition that, in the opinion of the study doctor, would make participation unsafe
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Investigated drugs

  • Pirtobrutinib

    (also known as LOXO-305) is a medication that belongs to the class of BTK inhibitors. It works by blocking specific proteins that help cancer cells grow and survive. This medication is being studied as a new treatment option for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma.

  • Venetoclax

    is a medication that works by blocking a protein called BCL-2, which helps cancer cells survive. By blocking this protein, venetoclax can cause cancer cells to die. It is already approved for treating certain types of blood cancers.

  • Rituximab

    is an antibody therapy that targets specific proteins (CD20) found on the surface of certain blood cancer cells. It helps the immune system identify and destroy these cancer cells. Rituximab has been used for many years to treat various types of blood cancers and autoimmune conditions.

What is already known about the treatment

  • Pirtobrutinib

    A novel oral Bruton's tyrosine kinase (BTK) inhibitor administered in tablet form that specifically targets blood cancer cells. This medication is currently being investigated in clinical trials for treating Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, particularly in patients who have received prior treatment. It works by blocking the BTK enzyme, which is essential for B-cell cancer growth and survival, and belongs to the class of targeted cancer therapy drugs.

  • Venetoclax

    An oral medication taken as tablets that functions as a selective B-cell lymphoma-2 (BCL-2) inhibitor, used in the treatment of blood cancers. It works by blocking the BCL-2 protein that helps cancer cells survive, effectively promoting cancer cell death, and is classified as a targeted therapy agent. This medication is already approved and well-established in the treatment of chronic lymphocytic leukemia.

  • Rituximab

    An intravenous monoclonal antibody medication that specifically targets the CD20 protein found on B-cells, making it effective in treating various blood cancers. It works by helping the immune system identify and destroy cancerous B-cells and is classified as a biological therapy agent. This medication has been widely used in cancer treatment for many years and has a well-documented safety profile.

Investigated diseases

  • Chronic Lymphocytic Leukemia

    A slow-growing blood cancer that starts in white blood cells called lymphocytes in the bone marrow. These abnormal cells gradually build up in the blood, bone marrow, and lymph nodes. The disease typically develops over months or years, with many people not showing symptoms in early stages. As it progresses, it can cause swollen lymph nodes, fatigue, and increased risk of infections. This condition sometimes occurs together with Small Lymphocytic Lymphoma, which is essentially the same disease but primarily affects the lymph nodes rather than the blood and bone marrow.

  • Small Lymphocytic Lymphoma

    A type of cancer that affects the lymphocytes, a kind of white blood cell that helps the body fight infection. The disease mainly involves the lymph nodes, causing them to become enlarged. It is considered the same disease as Chronic Lymphocytic Leukemia but with a different pattern of where the cancer cells collect in the body. People with this condition may experience fatigue, night sweats, and unexplained weight loss.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-507698-16-00Protocol codeLOXO-BTK-20022Estimated enrolment639 patientsSponsorLoxo Oncology Inc.

sourced from the EU Clinical Trials Register and site verification

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