Clinical Trials for Richter’s Syndrome
Richter’s syndrome is a serious transformation of chronic lymphocytic leukemia into a more aggressive form of lymphoma. Currently, 7 clinical trials are testing various treatment approaches for this condition across multiple European countries. These studies are investigating innovative therapies including targeted medications, immunotherapy combinations, and cell-based treatments to improve outcomes for patients whose disease has either returned after treatment or has not responded to previous therapies.
Clinical trial locations
- Austria
- Belgium
- France
- Germany
- Italy
- Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
- Study on the Safety and Effectiveness of Venetoclax, Atezolizumab, and Obinutuzumab for Patients with Richter Syndrome from Chronic Lymphocytic Leukemia
- Study on Brexucabtagene Autoleucel for Adults with Relapsed/Refractory Richter Transformation (RT)
- Study on the Effects of Acalabrutinib in Patients with Chronic Lymphocytic Leukemia, Richter’s Syndrome, or Prolymphocytic Leukemia
- Netherlands
- Poland
- Spain
- Sweden
Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
This trial is testing BGB-16673, an experimental BTK-degrader medication, in combination with other treatments for patients whose B-cell cancers have returned or not responded to previous therapies. The study is being conducted in Poland, Germany, and Italy.
Main inclusion criteria: Patients must be at least 18 years old with a confirmed diagnosis of relapsed or refractory B-cell malignancy. Participants need to have measurable disease and good physical function with an ECOG Performance Status of 0-1, meaning they can perform daily activities with minimal limitations. Adequate organ and kidney function is required. Women who can become pregnant must use effective birth control during the study and have a negative pregnancy test before starting treatment.
Main exclusion criteria: The study excludes patients under 18 years old and those with active central nervous system involvement from their cancer. Patients with uncontrolled infections, significant heart problems, severe kidney or liver issues, or who are pregnant or breastfeeding cannot participate. Those with a history of other cancers within the past 3 years, known HIV infection, active hepatitis B or C, or mental conditions that could interfere with study participation are also excluded.
Focus and goal: The study aims to find safe and effective treatment combinations for patients whose cancer has come back or did not respond to earlier treatments. It will be conducted in two parts: the first will determine the right dose of the drug combinations, while the second will further study how well these doses work and what side effects they may cause. Doctors will monitor patients’ health throughout, checking how well the treatment is working and tracking any side effects.
Investigational drugs: The trial uses BGB-16673, which works by breaking down a specific protein called BTK that is important in B-cell cancers. This medication is being studied in combination with other treatments including zanubrutinib, sonrotoclax, mosunetuzumab, obinutuzumab, and glofitamab. The medications are given as tablets taken by mouth or through intravenous infusion or subcutaneous injection.
Study of Glofitamab with Rituximab or Obinutuzumab and Drug Combination for Untreated Richter’s Syndrome Patients
This French trial evaluates a new treatment combination for patients who have not previously received treatment for Richter’s syndrome. The study is specifically designed for patients whose chronic lymphocytic leukemia has transformed into a more aggressive form.
Main inclusion criteria: Participants must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma that has transformed into diffuse large B-cell lymphoma. Patients must be between 18 and 80 years old with an ECOG performance status of 0 to 2. At least one measurable tumor or lymph node is required, or bone marrow involvement. Previous treatment for the underlying leukemia is allowed, but not for the transformation itself. Patients must have adequate blood health, liver function, heart health, and kidney function. A negative pregnancy test is required for women of childbearing potential, and all participants must agree to use effective birth control.
Main exclusion criteria: Patients who have already received treatment specifically for Richter’s syndrome cannot participate. Those who do not have the diffuse large B-cell lymphoma type are not eligible.
Focus and goal: The study aims to determine how well a combination treatment works in reducing the cancer. Participants will receive up to six cycles of treatment involving Glofitamab combined with either Rituximab or Obinutuzumab, along with the CHOP chemotherapy regimen (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). The medications are delivered through intravenous infusion, except for prednisone which is taken orally. Regular assessments will track the cancer’s response and monitor for side effects.
Investigational drugs: Glofitamab is a bispecific antibody that helps the immune system target and destroy cancer cells by connecting proteins on cancer cells with those on immune cells. Rituximab and Obinutuzumab also target specific proteins on cancer cells to help the immune system destroy them. The chemotherapy drugs (Cyclophosphamide, Doxorubicin, and Vincristine) work by slowing or stopping cancer cell growth, while Prednisone helps reduce inflammation and manage side effects.
Study of Mosunetuzumab and Drug Combination for Untreated Patients with Richter’s Syndrome
This Spanish trial explores the effectiveness of the M-CHOP treatment combination for patients who have not previously received treatment for Richter’s syndrome.
Main inclusion criteria: Patients must be adults between 18 and 79 years old with previously untreated Richter’s syndrome, specifically the diffuse large B cell variant, confirmed by medical criteria. Participants need to have CD20 positive disease confirmed by special tests. An ECOG performance score of 2 or less is required, meaning patients can perform most daily activities. Adequate bone marrow function and a creatinine clearance of at least 45 mL/min are necessary. Participants must have a life expectancy of more than 3 months and agree to use birth control to avoid pregnancy or fathering a child during the study.
Main exclusion criteria: Patients who have already received treatment for Richter’s syndrome cannot participate. Those outside the specified age range or who are part of a vulnerable population requiring special protection are not eligible.
Focus and goal: The study evaluates the M-CHOP combination, which includes mosunetuzumab, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide monohydrate, and prednisone. The treatment is structured in cycles with regular monitoring through imaging tests such as PET/CT scans. The primary goal is to achieve complete remission, meaning no detectable disease in the body. The study includes a comparison with a placebo to determine treatment effectiveness.
Investigational drugs: Mosunetuzumab is an experimental immunotherapy medication that targets specific proteins on cancer cells to help the immune system recognize and destroy them. CHOP is a combination of four chemotherapy drugs (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) that work together to kill cancer cells or stop them from growing. Most medications are given intravenously, except prednisone which is taken orally.
Study on Golcadomide for Patients with Relapsed or Refractory Large B-Cell Lymphoma in the Brain
This trial in the Netherlands and Belgium studies Golcadomide for treating lymphoma that affects the brain, including cases where the cancer has returned or not responded to previous treatments.
Main inclusion criteria: Patients must be at least 18 years old with a diagnosis of secondary central nervous system lymphoma, relapsed primary large B-cell lymphoma of the central nervous system, or refractory primary large B-cell lymphoma of the central nervous system. Cohort A participants must have received prior high-dose methotrexate-based chemotherapy. Cohort B participants must have aggressive malignant B-cell lymphoma with specific subtypes and central nervous system involvement confirmed by cerebrospinal fluid analysis, MRI evidence, or biopsy. A WHO performance status of 2 or less is required, along with adequate blood counts and willingness to follow study requirements.
Main exclusion criteria: The study excludes patients with secondary central nervous system lymphoma, relapsed primary large B-cell lymphoma of the central nervous system, and refractory primary large B-cell lymphoma of the central nervous system who do not meet the specific inclusion criteria.
Focus and goal: The study aims to evaluate whether Golcadomide can help reduce the cancer or achieve complete remission. Participants will receive the medication as a capsule taken by mouth. Regular assessments including blood tests and imaging will monitor treatment effects. The study will continue until 2028, examining how the medication behaves in the body, including its presence in spinal fluid compared to blood, and investigating genetic factors that might influence treatment response.
Investigational drugs: Golcadomide (CC-99282) is an experimental medication that interferes with specific pathways cancer cells use to grow and survive, thereby inhibiting their proliferation. It is being tested specifically for brain lymphomas and is administered orally.
Study on the Safety and Effectiveness of Venetoclax, Atezolizumab, and Obinutuzumab for Patients with Richter Syndrome from Chronic Lymphocytic Leukemia
This Italian trial tests a three-drug combination for patients with Richter syndrome, focusing on both safety and effectiveness of this treatment approach.
Main inclusion criteria: Participants must be 18 years or older with a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma with biopsy-confirmed transformation to diffuse large B cell lymphoma consistent with Richter’s Syndrome. An ECOG performance status of 2 or less is required. Patients must meet specific blood health criteria at screening, including adequate neutrophil counts, platelet counts, and hemoglobin levels, unless bone marrow involvement affects these values. Adequate blood clotting, kidney, and liver function are necessary. Women of childbearing potential must have a negative pregnancy test and agree to use effective birth control for specified periods after treatment.
Main exclusion criteria: Patients with other types of cancer unrelated to Richter syndrome, those who have had recent different cancer treatment, pregnant or breastfeeding women, and those with severe uncontrolled medical conditions are excluded. Patients with recent participation in other clinical trials, allergies to study medications, uncontrolled infections, or inability to follow study procedures are also not eligible.
Focus and goal: The study evaluates the combination of venetoclax, atezolizumab, and obinutuzumab to see if it can achieve a significant response rate. The study aims for at least 67% overall response rate by the end of the sixth treatment cycle. Regular assessments will monitor for side effects and treatment effectiveness, including complete remission rate, duration of response, progression-free survival, and overall survival.
Investigational drugs: Venetoclax is taken orally as tablets and works by targeting and blocking a specific protein that cancer cells need to survive. Atezolizumab is given through intravenous infusion and helps the immune system recognize and attack cancer cells by blocking a protective protein. Obinutuzumab, also given intravenously, targets specific proteins on cancer cell surfaces to help the immune system destroy these cells.
Study on Brexucabtagene Autoleucel for Adults with Relapsed/Refractory Richter Transformation (RT)
This multi-country trial (Netherlands, Austria, Germany, France, Spain, Italy, and Sweden) investigates a specialized cell therapy for adults whose disease has returned or not responded to previous treatments.
Main inclusion criteria: Participants must be 18 years or older with a confirmed diagnosis of relapsed or refractory Richter Transformation. At least one measurable lesion is required, and lesions previously treated with radiation can only be counted if they have grown again. Previous treatment side effects must be stable and improved to a mild level. An ECOG performance status of 0 or 1 is required, along with adequate blood and organ function. Patients must have confirmed CLL with transformation to diffuse large B-cell lymphoma. The disease must have returned or not responded after one line of therapy. Those who can have children must agree to use specific birth control methods.
Main exclusion criteria: Patients with different types of cancer unrelated to Richter Transformation, those with severe allergic reactions to similar treatments, uncontrolled infections, pregnancy or breastfeeding, significant heart problems, active hepatitis B, C, or HIV, recent other cancer treatments, or any medical condition making participation unsafe are excluded.
Focus and goal: The study evaluates brexucabtagene autoleucel, a CAR T-cell therapy that uses genetically modified immune cells to target and destroy cancer cells. The treatment involves taking a patient’s own T-cells, modifying them in a laboratory, and infusing them back to fight the cancer. The study monitors response rates, duration of response, time to disease progression, and overall survival.
Investigational drugs: Brexucabtagene Autoleucel is a CAR T-cell therapy involving modified immune cells specifically designed to recognize and attack cancer cells. Preparatory medications like cyclophosphamide and fludarabine may be given before the main treatment. The therapy is administered through intravenous infusion.
Study on the Effects of Acalabrutinib in Patients with Chronic Lymphocytic Leukemia, Richter’s Syndrome, or Prolymphocytic Leukemia
This Italian trial explores acalabrutinib for treating several types of blood cancers, including Richter’s Syndrome, focusing on finding the safest and most effective dose.
Main inclusion criteria: Participants must be 18 years or older with confirmed diagnoses of chronic lymphocytic leukemia, small lymphocytic lymphoma, Richter’s syndrome, or prolymphocytic leukemia that has relapsed or been resistant to at least two previous treatments. For certain groups, patients whose condition is worsening after initially responding to ibrutinib or who did not respond well to ibrutinib can participate. Patients must have measurable disease with at least one lymph node 2 cm or larger and active disease meeting specific criteria for needing treatment. An ECOG performance status of 2 or less is required, along with agreement to use highly effective birth control methods.
Main exclusion criteria: While the trial includes patients with Richter’s Syndrome, specific exclusion criteria relating to this condition were not detailed in the provided information beyond general exclusions for the study.
Focus and goal: The study aims to determine the safety and appropriate dosage of acalabrutinib through dose escalation. Participants receive the medication in increasing doses to find the most effective and safe amount. The study looks at how the body processes the medication and its effects on the disease, with regular monitoring including check-ups and tests to ensure safety and gather information on the medication’s impact. The trial is expected to continue until June 2027.
Investigational drugs: Acalabrutinib (ACP-196) is provided as film-coated tablets and hard capsules taken orally. It works by inhibiting Bruton’s tyrosine kinase, a protein crucial for cancer cell growth and survival. The medication is classified as a kinase inhibitor and represents a targeted therapy option for specific types of leukemia.
Summary
The seven clinical trials for Richter’s syndrome reflect diverse therapeutic approaches across Europe. A notable concentration of trials is occurring in Italy, which hosts four studies, while multiple trials are also active in Germany, France, the Netherlands, and Spain. This geographic distribution suggests strong European commitment to addressing this challenging condition.
The trials can be broadly categorized into three treatment approaches. First, several studies focus on combination immunotherapy and chemotherapy for newly diagnosed patients, such as the glofitamab and mosunetuzumab trials in France and Spain. Second, multiple trials target relapsed or refractory disease with innovative approaches including the venetoclax combination in Italy and the BGB-16673 study spanning Poland, Germany, and Italy. Third, an advanced cell therapy trial using brexucabtagene autoleucel is being conducted across seven countries, representing the most widespread study.
The investigational treatments vary considerably, from targeted oral medications like venetoclax and acalabrutinib to intravenous immunotherapies like glofitamab and obinutuzumab, and finally to sophisticated CAR T-cell therapy. Most trials focus on patients whose disease has returned or not responded to previous treatments, though some specifically target treatment-naive patients. This diversity of therapeutic options and trial designs offers hope for improved treatment outcomes across different patient populations and disease stages.
