Ongoing Clinical Trials for Diffuse Large B-Cell Lymphoma Recurrent
This article provides an overview of 8 ongoing clinical trials investigating new treatments for diffuse large B-cell lymphoma that has returned after previous therapy. Trials are taking place across multiple European countries and are testing various drug combinations, including novel targeted therapies, immunotherapies, and CAR T-cell approaches. (Also known as: Relapsed Diffuse Large B-Cell Lymphoma, Refractory DLBCL, RR DLBCL)
Clinical trial locations
- Austria
- Belgium
- Denmark
- France
- Germany
- Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
- Study on ALLO-647 and ALLO-501A for Adults with Relapsed or Refractory Large B-Cell Lymphoma
- Study on the Effectiveness and Safety of AZD0486 for Adults with Relapsed or Refractory Non-Hodgkin Lymphoma
- Italy
- Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
- Study of Rituximab, Gemcitabine, Dexamethasone, and Platinum with or without Selinexor for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Study on the Effectiveness and Safety of AZD0486 for Adults with Relapsed or Refractory Non-Hodgkin Lymphoma
- Study on the Safety and Effectiveness of ALLO-501A and ALLO-647 for Adults with Relapsed or Refractory Large B-Cell Lymphoma
- Netherlands
- Poland
- Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
- Study of Rituximab, Gemcitabine, Dexamethasone, and Platinum with or without Selinexor for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Study on the Effectiveness and Safety of Cytarabine, Tafasitamab, and Lenalidomide for Patients with Relapsed Diffuse Large B-Cell Lymphoma
- Spain
- Study of Mosunetuzumab and Polatuzumab Vedotin for Patients with Diffuse Large B-Cell Lymphoma After Initial Treatment or in Elderly/Unfit Untreated Patients
- Study of Rituximab, Gemcitabine, Dexamethasone, and Platinum with or without Selinexor for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Study on the Effectiveness and Safety of AZD0486 for Adults with Relapsed or Refractory Non-Hodgkin Lymphoma
- Study on the Safety and Effectiveness of ALLO-501A and ALLO-647 for Adults with Relapsed or Refractory Large B-Cell Lymphoma
- Sweden
Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
This trial is investigating BGB-16673, an experimental BTK-degrader medication, in combination with other drugs for patients with B-cell cancers that have returned or not responded to previous treatments. The trial is taking place in Poland, Germany, and Italy.
Main inclusion criteria: Participants must be at least 18 years old with confirmed relapsed or refractory B-cell malignancy and measurable disease. They must have good physical function with an ECOG Performance Status of 0-1 and adequate organ function. Kidney function requirements vary depending on the sub-study, with eGFR requirements of either ≥30 mL/min or ≥50 mL/min. Women of childbearing potential must use effective birth control and have a negative pregnancy test before starting treatment. Men must also use effective birth control during the study.
Main exclusion criteria: Patients under 18 years old, those with active central nervous system involvement from their cancer, previous treatment with BGB-16673, active uncontrolled infections, significant heart problems, severe kidney or liver problems, pregnant or breastfeeding women, recent history of other cancers, known HIV infection, active hepatitis B or C, recent major surgery, mental conditions that could interfere with participation, allergies to similar medications, uncontrolled high blood pressure, or other serious medical conditions are excluded.
Focus of the trial: The study aims to determine the safe dose of BGB-16673 when combined with other medications like zanubrutinib, sonrotoclax, mosunetuzumab, obinutuzumab, and glofitamab. The trial will evaluate how well these drug combinations work in treating relapsed or refractory B-cell malignancies and will monitor for side effects. Medications will be administered through oral tablets, intravenous infusion, or subcutaneous injection.
Investigational drug: BGB-16673 is an experimental BTK-degrader that works by breaking down a specific protein important in B-cell cancers. It is being studied in combination with other treatments to help patients whose B-cell blood cancers have either come back or did not respond well to previous treatments.
Study on Golcadomide for Patients with Relapsed or Refractory Large B-Cell Lymphoma in the Brain
This trial is evaluating Golcadomide for treating large B-cell lymphoma affecting the brain, particularly in cases where the cancer has returned or not responded to previous treatments. The study is being conducted in the Netherlands and Belgium.
Main inclusion criteria: Participants 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. For Cohort A, patients must have received prior high-dose methotrexate-based chemotherapy. For Cohort B, patients must have aggressive malignant B-cell lymphoma with central nervous system involvement confirmed through specific criteria. All participants must have a WHO performance status of 2 or less, adequate blood counts, kidney and liver function, and must be willing to follow the study requirements.
Main exclusion criteria: The exclusion criteria specifically mention that patients with 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 cannot participate, though this appears to conflict with the inclusion criteria and may reflect different cohort requirements.
Focus of the trial: The study aims to evaluate how well Golcadomide works in treating large B-cell lymphoma affecting the brain. Some participants may receive a placebo for comparison. The trial will monitor various outcomes including complete or partial remission rates, time to response, duration of response, overall survival, side effects, quality of life, drug levels in spinal fluid compared to blood, and genetic factors that might influence treatment response.
Investigational drug: Golcadomide is taken orally in capsule form. It is being tested to see if it can help reduce or eliminate cancer affecting the central nervous system in patients who have not responded to or have relapsed after previous treatments.
Study on the Effectiveness and Safety of AZD0486 for Adults with Relapsed or Refractory Non-Hodgkin Lymphoma
This trial is testing AZD0486, a monoclonal antibody, for treating Non-Hodgkin Lymphoma that has returned or not responded to previous treatments. The study is taking place in Italy, Germany, Sweden, Spain, France, and Denmark.
Main inclusion criteria: Participants must be between 18 and 80 years old at the time of signing consent. They must have an ECOG performance status of 0 to 2, meaning they can perform daily activities with minimal to moderate limitations. Patients must have relapsed or refractory disease after at least two previous treatments and a confirmed diagnosis of B-cell Non-Hodgkin Lymphoma according to WHO 2017 classification. The disease must be detectable on FDG imaging and measurable. Participants must have adequate liver, blood, kidney, and heart function.
Main exclusion criteria: Patients with cancer types other than Non-Hodgkin Lymphoma, those without relapsed or refractory disease, patients outside the specified age range, those unable to give informed consent, pregnant or breastfeeding women, those with interfering medical conditions, recent participants in other clinical trials, and those who have had certain interfering treatments or medications are excluded.
Focus of the trial: The study aims to learn how well AZD0486 works and how safe it is for patients with relapsed or refractory Non-Hodgkin Lymphoma. The treatment will be given through intravenous infusion. Researchers will monitor how the cancer responds to treatment, track side effects, and collect information on changes in tumor size, improvements in symptoms, and overall health effects.
Investigational drug: AZD0486 is a monoclonal antibody administered by intravenous infusion. It is designed to target specific proteins on cancer cells, helping the body’s immune system to fight the cancer more effectively.
Study on the Effectiveness and Safety of Cytarabine, Tafasitamab, and Lenalidomide for Patients with Relapsed Diffuse Large B-Cell Lymphoma
This trial is focused on studying aggressive blood cancers, specifically Diffuse Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma. The study aims to evaluate early second-line treatment guided by tumor DNA levels in the blood for patients who have experienced a relapse. The trial is being conducted in Poland.
Main inclusion criteria: Patients must have a diagnosis of DLBCL or HGBCL and be eligible for chemotherapy treatments like R-CHOP, R-CHOP-like, Pola-R-CHP, or DA-EPOCH-R. Test results including mutation analysis, circulating free DNA assessment, and PET-CT scans must be available. Patients must be at least 18 years old, have signed informed consent, have a PET/CT scan showing disease progression, and have an ECOG performance status of 0-2 or 3 if due to disease progression. Effective contraception is required during and after the trial, and women of childbearing age must have a negative pregnancy test. Patients must provide tissue samples if needed and be in complete remission confirmed by PET-CT after first-line treatment.
Main exclusion criteria: Patients with other unrelated cancer types, those who have not completed previous treatments or recovered from side effects, those with severe heart problems or uncontrolled high blood pressure, active infections requiring treatment, pregnant or breastfeeding women, those with allergic reactions to similar treatments, other serious medical conditions that could interfere with the study, and those unable to follow study procedures or attend required visits are excluded.
Focus of the trial: The trial involves medications including Cytarabine, Tafasitamab, Lenalidomide, Dexamethasone, Cisplatin, Bendamustine Hydrochloride, Polatuzumab Vedotin, and Rituximab. The study will monitor overall response rates and significant side effects, conduct regular blood tests to measure circulating tumor DNA, perform PET-CT scans to monitor disease progression, and evaluate quality of life using questionnaires.
Investigational approach: Cell-free circulating tumor DNA found in the blood is used to help decide when to start a new treatment. By checking the levels of this DNA, doctors can determine if the cancer is coming back and whether it is time to begin a second round of treatment, aiming to catch the cancer early and potentially improve outcomes.
Study of Mosunetuzumab and Polatuzumab Vedotin for Patients with Diffuse Large B-Cell Lymphoma After Initial Treatment or in Elderly/Unfit Untreated Patients
This trial is exploring treatments for Diffuse Large B-Cell Lymphoma using Mosunetuzumab and Polatuzumab Vedotin. The study is being conducted in Poland and Spain and involves different patient groups depending on their treatment history and health status.
Main inclusion criteria: For all groups, patients must have at least one measurable lymph node lesion larger than 1.5 cm or extranodal lesion larger than 1.0 cm, and an ECOG Performance Status of 0, 1, or 2. For Cohort A, patients must have had one previous chemotherapy treatment and shown stable disease or partial response. For Cohorts B and C, elderly or unfit patients must meet specific age and health criteria, including difficulties with daily activities or health issues that prevent them from receiving standard chemotherapy. Patients in Cohorts B and C with initially poor performance status may be reconsidered if their condition improves after initial treatment.
Main exclusion criteria: Patients with cancer types other than DLBCL, those without first-line therapy for DLBCL, serious medical conditions that might interfere with study treatment, pregnant or breastfeeding women, active infections requiring treatment, recent history of other cancers, certain disallowed prior treatments, known allergies to study drugs, history of certain heart, lung, liver, kidney, blood, immune system, neurological, or psychiatric problems, and inability to comply with study procedures are excluded.
Focus of the trial: The study evaluates the effectiveness and safety of Mosunetuzumab either alone or in combination with Polatuzumab Vedotin. Cohort A receives Mosunetuzumab intravenously after initial treatment. Cohort B includes elderly or unfit patients receiving Mosunetuzumab intravenously. Cohort C involves elderly or unfit patients receiving Mosunetuzumab subcutaneously combined with Polatuzumab Vedotin intravenously. The trial monitors treatment effectiveness through imaging tests like PET-CT scans and tracks side effects.
Investigational drugs: Mosunetuzumab is being tested both as consolidation therapy after first-line treatment and as monotherapy or combination therapy in elderly or unfit patients. It works by engaging T-cells to target and destroy cancerous B-cells. Polatuzumab Vedotin is an antibody-drug conjugate being studied in combination with Mosunetuzumab, designed to deliver cytotoxic agents directly to cancer cells.
Study of Rituximab, Gemcitabine, Dexamethasone, and Platinum with or without Selinexor for Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
This trial is investigating whether adding Selinexor to a standard treatment combination improves outcomes for patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma. The study is taking place in Italy, Spain, and Poland.
Main inclusion criteria: Patients must be 18 years or older with an estimated life expectancy of more than 3 months. Primary refractory DLBCL patients who did not respond or relapsed within 6 months of first treatment are allowed. Patients must agree to use highly effective contraception during the study and for 12 months afterward. Female patients must have a negative pregnancy test and agree to use effective contraception. Male patients must agree not to donate sperm. Patients must have confirmed diagnosis of de novo DLBCL or transformed DLBCL from indolent lymphoma, have received 1 to 3 prior treatments that did not work, have PET positive measurable disease, not be intended for stem cell transplantation or CAR-T cell therapy, and have adequate bone marrow, liver, kidney function, and ECOG performance status of 2 or less.
Main exclusion criteria: Patients with another uncontrolled cancer, recent heart attack or severe heart problems, active infections requiring antibiotics, pregnant or breastfeeding women, known allergies to study drugs, recent major surgery, conditions affecting food or medicine absorption, other serious illnesses affecting safety, current participation in another clinical trial, and certain recent lymphoma treatments are excluded.
Focus of the trial: The study compares treatment with R-GDP (Rituximab, Gemcitabine, Dexamethasone, and Platinum) alone versus R-GDP combined with Selinexor. The first phase focuses on response rates, while the second phase looks at progression-free survival. Selinexor is taken as a tablet by mouth, and some patients receive a placebo for comparison.
Investigational drugs: The trial tests a combination of established medications including Rituximab (which targets specific proteins on cancer cells), Gemcitabine (a chemotherapy drug interfering with cancer cell DNA), Dexamethasone (a steroid reducing inflammation), and Platinum-based drugs (which damage cancer cell DNA). Selinexor is an experimental treatment that blocks a protein helping cancer cells grow and survive, and is being tested to see if adding it improves outcomes.
Study on ALLO-647 and ALLO-501A for Adults with Relapsed or Refractory Large B-Cell Lymphoma
This trial is testing a new treatment approach combining ALLO-647 and ALLO-501A CAR T-cell therapy for Large B-Cell Lymphoma that has returned or not responded to previous treatments. The study is being conducted in Germany, Belgium, and Austria.
Main inclusion criteria: Patients must have confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse, have disease that can be measured, have disease that has returned or not responded after at least two different chemotherapy treatments, have ECOG performance status of 0 or 1, no significant donor-specific anti-HLA antibodies at screening, and adequate blood cell counts and organ function.
Main exclusion criteria: Patients with any other type of cancer besides Large B-Cell Lymphoma, those who have had different cancer treatment within the last 4 weeks, those with severe heart problems, uncontrolled infections, pregnant or breastfeeding women, history of severe allergic reactions to similar treatments, active hepatitis B or C or HIV infection, recent stem cell transplant within 3 months, and any condition the study doctors believe would make participation unsafe are excluded.
Focus of the trial: The study aims to evaluate whether adding ALLO-647 to the standard preparation regimen of Fludarabine and Cyclophosphamide before receiving ALLO-501A CAR T-cell therapy improves outcomes. The trial will monitor how well the cancer responds, how long the response lasts, safety, and side effects.
Investigational drugs: Fludarabine and Cyclophosphamide are chemotherapy drugs used to prepare the body by lowering certain blood cell counts, making space for new therapy. ALLO-647 is designed to help the body accept the new cells by reducing immune response. ALLO-501A is the main CAR T-cell therapy, using specially modified cells to target and destroy cancer cells.
Study on the Safety and Effectiveness of ALLO-501A and ALLO-647 for Adults with Relapsed or Refractory Large B-Cell Lymphoma
This trial is evaluating the safety and effectiveness of ALLO-501A, a type of CAR T-cell therapy, combined with ALLO-647 for treating Large B-Cell Lymphoma that has returned or not responded to previous treatments. The study is taking place in Spain and Italy.
Main inclusion criteria: Patients must have confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse according to WHO 2017 guidelines, at least one measurable tumor at study entry, disease that has returned or not responded after at least two different chemotherapy treatments, ECOG performance status of 0 or 1, no significant donor-specific anti-HLA antibodies at screening, and adequate blood cell counts and organ function.
Main exclusion criteria: Patients with other cancer types besides Large B-Cell Lymphoma, those without relapsed or refractory disease, patients outside the specified age range, those unable to give informed consent or understand study requirements, pregnant or breastfeeding women, certain medical conditions that might interfere with study treatment, recent participation in another clinical trial, and those who have had certain interfering treatments or medications are excluded.
Focus of the trial: The study evaluates ALLO-501A, an anti-CD19 allogeneic CAR T-cell therapy, combined with ALLO-647, an anti-CD52 monoclonal antibody. Participants receive Fludarabine and Cyclophosphamide to prepare the body, followed by the main ALLO-501A and ALLO-647 treatments through intravenous infusion. Supportive care medications are provided to manage side effects. The trial monitors cancer response, treatment effectiveness, side effects, and includes regular follow-up visits with physical exams, blood tests, and imaging studies.
Investigational drugs: ALLO-501A uses specially modified CAR T-cells designed to target and destroy cancer cells in Large B-Cell Lymphoma. ALLO-647 is a monoclonal antibody that helps prepare the body to receive the ALLO-501A therapy by targeting certain immune cells, creating a better environment for the CAR T-cell therapy to work effectively.
Summary
These eight ongoing clinical trials represent diverse approaches to treating recurrent diffuse large B-cell lymphoma across multiple European countries. The trials are concentrated primarily in Western and Central European nations, with Italy, Spain, and Poland hosting the most studies. Germany, Belgium, and several other countries are also active participants in this research.
The trials explore several therapeutic strategies, including novel targeted therapies like BGB-16673 and Selinexor, immunotherapies such as Mosunetuzumab and Polatuzumab Vedotin, and advanced CAR T-cell approaches with ALLO-501A combined with ALLO-647. Some studies focus on combination treatments adding experimental drugs to established regimens, while others investigate entirely new therapeutic approaches. Several trials are examining treatments specifically for patients whose cancer has spread to the central nervous system or for elderly and unfit patients who cannot tolerate standard intensive chemotherapy.
Common eligibility requirements across most trials include confirmed diagnosis of relapsed or refractory disease after at least two prior treatments, adequate organ function, good performance status, and effective contraception requirements. Most trials exclude patients with active uncontrolled infections, severe organ dysfunction, pregnancy, or recent participation in other clinical trials. The research represents an important effort to develop new treatment options for patients with limited alternatives after standard therapies have failed.
