Not yet recruitingRare disease

Study of pirtobrutinib plus epcoritamab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma

Verified siteRegistered drugNo placebo

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

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

The study focuses on people whose chronic lymphocytic leukemia or small lymphocytic lymphoma has come back after earlier treatment. These are types of blood cancer that affect white blood cells and can cause fatigue, infections, and swollen lymph nodes. The treatment being tested combines an oral tablet called pirtobrutinib, taken by mouth, with an injectable medicine called epcoritamab. The tablet works by blocking a protein that helps cancer cells grow, while the injection is designed to bring the body’s immune cells into contact with the cancer cells so they can destroy them.

The purpose of the trial is to evaluate whether the combination of these two medicines is safe and can improve how long the disease stays under control. Participants will first take the oral tablet alone for three treatment cycles, then the injection will be added while the tablet continues, for a total of about two years of therapy. Throughout the study, regular doctor visits, blood tests, and imaging scans will be performed to watch for side effects, check the amount of cancer in the blood and bone marrow, and assess overall health.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Start pirtobrutinib monotherapy
You will take pirtobrutinib tablets at a dose of 200 mg by mouth each day. each cycle is about 4 weeks long, and you will continue this treatment for the first three cycles (approximately 12 weeks).
During this period you will attend clinic visits for blood tests and safety checks before the next medication is added.
Step 2
Safety assessment before adding epcoritamab
After completing three cycles of pirtobrutinib, doctors will review your blood test results and any side effects to ensure it is safe to start the second medication.
If the safety review is satisfactory, the study will move to the combination phase.
Step 3
Start combination therapy with epcoritamab
You will receive an injection of epcoritamab at a dose of 48 mg. the injection is given under medical supervision at each study visit.
You will continue to take pirtobrutinib 200 mg daily at the same time.
The combination will be administered for up to 12 cycles (about 48 weeks). each cycle lasts roughly 4 weeks.
Step 4
Continue pirtobrutinib after epcoritamab stops
After the 12‑cycle combination period, epcoritamab injections are stopped, but you keep taking pirtobrutinib 200 mg daily.
Pirtobrutinib treatment continues until a total of 24 cycles are completed (approximately 96 weeks from the start of therapy).
Step 5
Regular monitoring during treatment
Throughout the trial you will attend clinic visits every cycle for blood draws to check disease status and side effects.
Periodic bone‑marrow samples may be taken to assess the depth of disease response.
You will also complete quality‑of‑life questionnaires that ask about how you feel day‑to‑day.
Step 6
Final evaluation after last cycle
Once the 24th cycle of pirtobrutinib is finished, a final set of assessments including blood tests, bone‑marrow examination, and imaging will be performed.
The results will be used to determine overall response and long‑term outcomes.

Who can join the trial?

16 criteria

You have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that has either come back after treatment (relapsed) or did not respond to at least one prior systemic (body‑wide) therapy.
You are willing and able to keep all study appointments and follow the study procedures.
You can understand the study and give permission to take part, known as informed consent.
You have signed a written informed consent form.
Your doctor says you need treatment based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, which are guidelines for when CLL treatment is required.
You are 18 years of age or older.
Your overall health status, measured by the Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) performance status, is 0, 1, or 2 (meaning you are fully active or able to carry out light activities).
Your bone‑marrow (BM) function is adequate, shown by:
- Hemoglobin level higher than 5 mmol/L (or more than 8 g/dL) – a measure of the blood’s ability to carry oxygen.
- Absolute neutrophil count above 1.0 × 10⁹/L – a count of a type of white blood cell that fights infection.
- Platelet count above 30 × 10⁹/L – platelets help blood clot.
- Your kidney function is sufficient, with an estimated glomerular filtration rate (eGFR) of at least 45 mL/min, which indicates how well the kidneys filter waste.
- Your liver function is within acceptable limits:
  - AST and ALT (enzymes that show liver health) are no more than three times the normal upper limit.
  - Bilirubin (a substance processed by the liver) is no more than 1.5 times the normal upper limit, unless the increase is due to a harmless condition called Gilbert’s syndrome or a controlled autoimmune hemolytic anemia.
  - Your blood clotting tests are normal:
    
    Prothrombin time (PT) / International Normalized Ratio (INR) less than 1.5 times the normal upper limit.
    Activated partial thromboplastin time (aPTT) less than 1.5 times the normal upper limit.
    You test negative for hepatitis B and C infections, meaning you have no hepatitis B surface antigen (HBsAg), no hepatitis B core antibody (anti‑HBc), and no hepatitis C antibody in your blood.

Who cannot join the trial?

36 criteria

You have received any cancer medicines such as targeted drugs, experimental agents, therapeutic antibodies, or chemotherapy within the last 5 drug half‑lives (the time it takes for the drug level to drop by half) or 2 weeks, whichever is shorter.
You have had an immunoconjugated antibody (an antibody linked to a toxin) within the last 10 weeks or 5 half‑lives, whichever is shorter.
You received broad field radiation that treated at least 30% of the bone marrow or whole‑brain radiation within the past 14 days.
You received limited palliative radiation (used to relieve symptoms) within the past 7 days.
You have previously been treated with a CD3 × CD20 bispecific antibody.
You have taken pirtobrutinib (the study drug) within the past 24 months.
You received CAR‑T‑cell therapy (a type of personalized cell therapy) within the past 100 days, or you need anti‑cytokine medication for side effects from that therapy, or you still have neurological side effects greater than Grade 1.
You have used any other experimental drug or therapy within 28 days before joining the study.
You have another cancer besides CLL/SLL that is not in remission, unless it was a non‑melanoma skin cancer or another tumor that was cured at least 1 year ago and does not need systemic treatment.
You had major surgery (major operation) within 28 days before joining the study.
You are pregnant or are breastfeeding.
You have known involvement of the central nervous system (brain or spinal cord) by disease.
You are a fertile man or woman of child‑bearing potential unless you are permanently sterile, at least 2 years past menopause, or you agree to use a highly effective birth‑control method during treatment and for the required time after the last dose.
You plan to donate eggs (ova) or sperm for assisted reproduction during the study or for the specified time after the last dose.
You are currently taking part in another clinical trial that uses study medication.
You have any psychological, family, social, or geographical situation that could prevent you from following the study schedule.
You have had a previous allogeneic stem‑cell transplant (donor‑derived) or a solid‑organ transplant.
You have severe heart disease (CTCAE Grade III‑IV) such as unstable angina, recent heart attack (within 3 months), left‑ventricular ejection fraction ≤ 40 %, advanced heart‑failure symptoms (NYHA Class III or higher), uncontrolled abnormal heart rhythms, or a baseline ECG showing a QTcF interval > 480 ms.
You have a history of confirmed progressive multifocal leukoencephalopathy (PML), a serious brain infection.
You have an active autoimmune disease that requires strong immune‑suppressing medication (except low‑dose prednisone up to 20 mg daily).
You are allergic to xanthine oxidase inhibitors or rasburicase (medicines used to lower uric acid).
You have a seizure disorder that needs ongoing medication.
You have active tuberculosis (TB) or completed TB treatment within the past 12 months.
You are taking blood‑thinning medication such as warfarin, vitamin K antagonists, or phenprocoumon.
You have had severe allergic or anaphylactic reactions to anti‑CD20 antibodies, bispecific antibodies, or any component of the study drugs.
You have a history of bleeding disorders (bleeding diathesis).
You have an active infection (bacterial, viral, fungal, mycobacterial, parasitic) within 2 weeks before the first dose, except for nail‑bed fungal infections.
You have an active cytomegalovirus (CMV) infection.
Your CLL has transformed into Richter’s transformation (a more aggressive form of lymphoma).
You are known to be HIV‑positive.
You had a stroke or bleeding in the brain within the past 6 months.
You have severe lung disease (CTCAE Grade III‑IV).
You have severe neurological or psychiatric disease (CTCAE Grade III‑IV).
You have nerve damage (neuropathy) greater than Grade II.
You have difficulty swallowing pills or have a gastrointestinal condition that would prevent the medication from being absorbed.
You received a live vaccine (such as measles, mumps, rubella) within 28 days before registration.

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Albert Schweitzer Ziekenhuis
Verified
Dordrecht, The Netherlands
Amphia Hospital
Verified
Breda, The Netherlands
Amsterdam UMC
Responsive
Amsterdam, The Netherlands

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not yet recruiting

Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

Jaypirca
is an oral tablet taken by mouth. It contains the active ingredient pirtobrutinib, which works by blocking a protein that helps certain blood cancer cells grow. In this study, patients start by taking this tablet alone for a few cycles, and then it is continued together with another medicine. The goal is to see how safe it is and whether it helps control the disease.
Epcoritamab
(also known as GEN3013) is given as an injection. It is a special type of antibody that can bind to both cancer cells and immune cells, helping the immune system recognize and attack the cancer. In the trial, after the first few cycles of the oral tablet, patients begin receiving this injection for several cycles. The purpose is to test if adding it improves the treatment results.

What is already known about the treatment

Pirtobrutinib
This medication is taken as a 100 mg film‑coated tablet taken by mouth. It is an approved Bruton tyrosine kinase (BTK) inhibitor used for treating relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It works by binding to the BTK enzyme inside cancer cells, blocking signals that tell the cells to grow and survive. Pharmacologically, it belongs to the class of BTK inhibitors.
Epcoritamab
This drug is supplied as a 48 mg solution for injection that is given subcutaneously to deliver the medication under the skin. It is a bispecific antibody that is currently approved for certain B‑cell cancers and is being studied for CLL/SLL in this trial. It connects T‑cells (via CD3) to cancer B‑cells (via CD20), directing the immune system to attack the tumor cells. Its pharmacological class is a bispecific T‑cell engager (BiTE) antibody.

Investigated diseases

Chronic lymphocytic leukemia (CLL)
This is a slow‑growing blood cancer where a large number of abnormal white blood cells (lymphocytes) accumulate in the blood and bone marrow. Over time the number of these cells can increase, gradually reducing the production of normal blood cells. The disease may stay stable for months or years before showing noticeable changes in cell counts. As more abnormal cells build up, the bone marrow can become crowded, affecting its ability to make healthy cells. The condition can spread to the spleen and other organs, leading to larger organ size.
Small lymphocytic lymphoma (SLL)
This is a type of cancer that primarily forms solid tumors in the lymph nodes and other lymphoid tissues. It involves the same abnormal lymphocytes seen in CLL, but they are mostly located in tissue rather than the blood. The lymph nodes may slowly enlarge as the disease progresses. Over time, the abnormal cells can spread to the blood and bone marrow, making the disease resemble CLL. The growth is generally gradual, and patients may not notice symptoms for an extended period.