Evaluating the efficacy of pirtobrutinib and epcoritamab in patients with untreated Richter transformation of chronic lymphocytic leukemia

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What is this study about?

This study is being conducted to evaluate the effectiveness of certain medications in patients diagnosed with Richter Transformation, a condition where Chronic Lymphocytic Leukemia, a type of blood cancer, changes into a more aggressive form of Diffuse Large B-Cell Lymphoma. The research compares a combination of two new drugs, pirtobrutinib and epcoritamab, against a standard treatment regimen known as R-(mini)-CHOP.

The comparison group receives the standard treatment, which consists of several different medications including rituximab, doxorubicin hydrochloride, vincristine, cyclophosphamide, and prednisolone. In the study group, participants receive pirtobrutinib as an oral tablet and epcoritamab as a subcutaneous injection, which is a method of delivering medication just under the skin. The study aims to determine how well these different treatment options work to control the disease.

Who Can Join the Study?

A confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), which are types of blood cancers.
You must be at least 18 years old.
An ECOG performance status of 0 to 2, which is a scale used to measure how well a person can perform daily activities and their general level of physical functioning.
An expected life expectancy of at least 3 months.
Women who may become pregnant and their partners must agree to use highly effective birth control during the treatment and for 1 month after the final dose.
The ability and willingness to sign a written informed consent form, which is a document explaining the study details, and to follow the study schedule.
A confirmed diagnosis of DLBCL-type Richter transformation, which is a change in the type of blood cancer cells.
You must have not previously received treatment for the Richter transformation, though previous treatment for CLL or certain steroids is allowed.
A required washout period, which is a specific amount of time you must wait after your last dose of other medications or radiation before starting this study. This includes:
- Specific waiting times for targeted agents, investigational drugs, monoclonal antibodies, or chemotherapy.
- At least 14 days after broad field radiation (radiation covering a large area of the bone marrow or brain).
- At least 7 days after palliative limited field radiation (radiation used to relieve symptoms in a small area).
Any previous side effects from treatments must have improved to Grade 1 or less, meaning they are very mild, though hair loss is an exception.
A creatinine clearance of at least 40ml/min, which is a test used to check how well your kidneys are filtering your blood.
Adequate liver function, measured by levels of bilirubin and enzymes called AST and ALT in the blood.
A neutrophil count of at least 1.0 G/l, which are white blood cells that help fight infections.
A hemoglobin (Hb) level of at least 8 g/dl, or at least 6.0 g/dl if the cancer is in the bone marrow. Hemoglobin is the part of red blood cells that carries oxygen.
A platelet count of at least 50 G/l, or at least 30,000 if the cancer is in the bone marrow. Platelets are blood cells that help with clotting.
Adequate coagulation, which means your blood can clot properly. This is measured by tests called aPTT, PTT, PT, or INR.
Negative test results for Hepatitis B, Hepatitis C, and HIV within 6 weeks before joining the study.

Who Cannot Join the Study?

Patients who have received prior radiation therapy (a treatment that uses high-energy rays to kill cancer cells) or have used corticosteroids (a type of steroid medicine used to reduce inflammation) for more than 10 days at a high dose.
People with significant cardiovascular disease, which means serious heart problems. This includes:
- Unstable angina (chest pain that occurs unpredictably) or acute coronary syndrome (a sudden reduction of blood flow to the heart) within the last 2 months.
- A history of myocardial infarction (a heart attack) within the last 3 months.
- A left ventricular ejection fraction (LVEF) of 40% or less in the last 12 months, which is a measurement of how much blood the heart pumps out with each beat.
- Heart failure classified as Grade 3 or higher on the NYHA scale (a system used to classify the severity of heart failure symptoms).
- Arrhythmias (irregular heartbeats) that are not controlled or cause symptoms.
- A prolonged QT interval, which is a measurement of the time it takes for the heart muscle to recharge between beats.
Patients who cannot swallow pills or have gastrointestinal issues (problems with the digestive system), such as malabsorption syndrome (the inability to absorb nutrients from food), having had parts of the stomach or small intestine removed, having had weight loss surgery, or having inflammatory bowel disease or a blockage in the bowels.
Patients with other types of cancer that are not being successfully treated, unless the cancer is stable and the patient is expected to live for more than 2 years.
Patients with an active infection (an ongoing illness caused by germs, such as a fever or positive blood tests) that requires medicine to treat.
Patients with a suspicion of CMV (a type of virus) unless they have been tested and are eligible based on specific results.
Patients with significant comorbidities (other medical conditions) or organ system impairment (when an organ like the liver or kidneys is not working correctly) that might make the study unsafe or interfere with how the study drugs work.
Patients who need to take medicines that affect the CYP3A4 enzyme (a specific protein in the liver that helps break down many drugs).
Patients with an active infection of HIV or Hepatitis B or C (viruses that affect the immune system or the liver) unless they meet specific testing requirements.
Patients who have had major surgery within 4 weeks of the first dose of the study medicine.
Patients who have used investigational agents (experimental drugs or treatments currently being studied) within 28 days of joining the study.
Patients whose disease has progressed (gotten worse) after using certain types of BTK inhibitors or CD20 targeting antibodies (specific types of targeted cancer treatments).
People with a known hypersensitivity (an allergic reaction) to the study medicines or any of their ingredients.
Pregnant women, nursing mothers, or anyone planning to become pregnant during the study or for one month after the last dose.
Women of childbearing potential or fertile men who are not surgically unable to have children, unless they agree to use two reliable forms of contraception (methods to prevent pregnancy) during and after the study.
Patients who have received a live vaccine (a vaccine that uses a weakened form of a germ) less than 28 days before starting.
People who are legally incapable (unable to make their own legal decisions), prisoners, or people living in institutions by court order.
People who have a relationship of dependence on the researchers or the company sponsoring the study.
Patients whose disease has changed into Hodgkin’s lymphoma or other specific types of lymphoma (cancer of the lymph nodes/immune system).
Patients who have had a stem cell transplant or CAR T-cell therapy (specialized immune cell treatments) within the last 100 days, or those with graft versus host disease (GVHD) (a condition where transplanted cells attack the body).
Patients with cytopenia (a low count of blood cells, such as red cells, white cells, or platelets) that has not recovered after a transplant.
Patients with known involvement of the CNS (the central nervous system, which includes the brain and spinal cord) by their disease.
Patients confirmed to have PML (a rare and serious brain infection caused by a virus).
Patients with autoimmune cytopenia (a condition where the immune system attacks its own blood cells) that is not responding to medicine.
Patients at high risk of bleeding, such as those with hemophilia (a disorder where blood does not clot normally), those taking certain anticoagulants (blood thinners), or those who have had a stroke or brain bleed in the last 6 months.
Patients who require supplemental oxygen (extra oxygen delivered through a mask or tubes).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Medizinische Universitaet Innsbruck	Innsbruck	Austria
Technische Universitaet Dresden	Dresden	Germany
Medical University Of Vienna	Vienna	Austria
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany

Other Sites

Site Name	City	Country
Universitaetsklinikum Schleswig-Holstein AöR	Kiel	Germany
University Hospital Galway	Galway	Ireland
Rigshospitalet	Copenhagen	Denmark
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
Beaumont Hospital	Dublin	Ireland
Uczxdmnggx Hgilrair Cnfyfjk	Cologne	Germany
Gyvncb Udwjrxonpf Fbyqsutio	Frankfurt	Germany

Trial status

Country	Status	Recruitment Start
Austria	Not yet recruiting	01.04.2026
Denmark	Not yet recruiting	01.04.2026
Germany	Not yet recruiting	01.04.2026
Ireland	Not yet recruiting	01.04.2026

Trial locations

Investigated drugs:

Pirtobrutinib is an oral medication used as part of the experimental treatment group to target specific proteins that help certain cancer cells grow.

Epcoritamab is an injectable medication given under the skin as part of the experimental treatment group to help the immune system recognize and attack cancer cells.

Doxorubicin is a chemotherapy drug given through an IV infusion as part of the standard comparison treatment group.

Prednisolone is a steroid medication taken by mouth as part of the standard comparison treatment group.

Vincristine is a chemotherapy drug given by injection as part of the standard comparison treatment group.

Rituximab is a medication given through an IV infusion as part of the standard comparison treatment group to target specific cells in the immune system.

Cyclophosphamide is a chemotherapy drug given through an IV infusion as part of the standard comparison treatment group.

Investigated diseases:

Chronic lymphocytic leukaemia

Chronic lymphocytic leukemia – This is a type of cancer that starts in the white blood cells known as lymphocytes. These abnormal cells build up in the blood, bone marrow, and lymph nodes. The disease often progresses slowly over many years. As it develops, the body may struggle to produce enough healthy blood cells.

Diffuse large B-cell lymphoma – This is a fast-growing type of cancer that affects the B lymphocytes, which are a type of white blood cell. It occurs when these cells undergo abnormal changes and begin to multiply uncontrollably. The disease typically moves through the lymphatic system and can affect other organs. It is characterized by the rapid enlargement of lymph nodes.

Richter transformation – This refers to a process where a slow-growing type of leukemia changes into a more aggressive form of lymphoma. It most commonly occurs in individuals who already have chronic lymphocytic leukemia. The transition leads to a more rapid spread of cancer cells throughout the body. It represents a significant change in the behavior and speed of the disease.

Trial ID:

2024-513445-37-00

Protocol code:

CLLRT2

Trial Phase:

Therapeutic confirmatory (Phase III)

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Evaluating the efficacy of pirtobrutinib and epcoritamab in patients with untreated Richter transformation of chronic lymphocytic leukemia

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?