Ongoing Clinical Trials for Mantle Cell Lymphoma Refractory
There are currently 6 clinical trials investigating new treatments for mantle cell lymphoma that has not responded to previous therapies or has returned after treatment. These studies are testing innovative approaches including CAR-T cell therapies, targeted medications, and combination treatments across several European countries including Belgium, Czechia, France, Germany, Italy, Netherlands, Poland, and Spain.
Clinical trial locations
- Belgium
- Czechia
- France
- Germany
- Italy
- Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
- Study on KTE-X19 CAR-T Cell Therapy for Patients with Relapsed or Refractory Mantle Cell Lymphoma Responding Partially to Ibrutinib
- Study on Loncastuximab Tesirine for Patients with Relapsed or Refractory Mantle Cell Lymphoma After Immunochemotherapy with Rituximab, Bendamustine, and Cytarabine
- Study of BGB-11417 for Patients with Relapsed or Refractory Mantle Cell Lymphoma
- Netherlands
- Poland
- Spain
Study of BGB-16673 in combination with drug therapy for patients with relapsed or refractory B-cell malignancies
This trial tests BGB-16673, a new type of medication called a BTK-degrader, in combination with other treatments for patients whose B-cell blood cancers have returned or not responded to previous therapies.
Main inclusion criteria: Participants must be at least 18 years old and have a confirmed diagnosis of relapsed or refractory B-cell malignancy that can be measured. They must have good physical function with an ECOG Performance Status of 0-1, meaning they can perform daily activities with minimal limitations. Adequate organ function is required, including kidney function with eGFR of at least 30-50 mL/min depending on the sub-study. Women who can become pregnant must use effective birth control and have a negative pregnancy test before starting treatment. Men who are not sterile must also use birth control during the study.
Main exclusion criteria: People under 18 years old cannot participate. The study excludes those with active central nervous system involvement, uncontrolled infections, significant heart problems, severe kidney or liver problems, or other cancers within the past 3 years. Pregnant or breastfeeding women are not eligible. People with HIV, active hepatitis B or C, uncontrolled high blood pressure, or recent major surgery are also excluded.
Focus: The study aims to find safe and effective treatment combinations for relapsed or refractory B-cell malignancies. It will be conducted in two parts: first determining the right dose of the drug combinations, then studying how well these doses work and tracking any side effects. Throughout the study, doctors will monitor patients’ health, check treatment effectiveness, and measure remaining cancer cells in some patients.
Investigational drugs: The main medication is BGB-16673, a BTK-degrader taken as tablets by mouth. Depending on the treatment group, participants may also receive zanubrutinib (oral capsules), obinutuzumab (intravenous infusion), glofitamab (intravenous infusion), or mosunetuzumab (injection under the skin).
Study on KTE-X19 CAR-T Cell Therapy for Patients with Relapsed or Refractory Mantle Cell Lymphoma Responding Partially to Ibrutinib
This trial evaluates KTE-X19, a CAR-T cell therapy that modifies a patient’s own immune cells to better recognize and attack cancer cells in mantle cell lymphoma patients who have shown a partial response to Ibrutinib treatment.
Main inclusion criteria: Participants must be adults between 18 and 75 years old with a confirmed diagnosis of mantle cell lymphoma. They must have experienced relapse or have disease that didn’t respond to at least one previous treatment before starting Ibrutinib, and currently be receiving Ibrutinib without tolerability issues. A confirmed partial response after at least 6 months of Ibrutinib treatment is required. Participants must have adequate blood counts, liver function, kidney function (creatinine clearance at least 60 mL/min), heart function (ejection fraction at least 50%), and lung function (oxygen saturation greater than 92%). Women who can have children must have a negative pregnancy test and use effective birth control.
Main exclusion criteria: Patients whose disease has not returned or worsened, those not currently receiving Ibrutinib as single therapy, and those not in partial remission during Ibrutinib therapy cannot participate. People outside the specified age range or unable to receive the KTE-X19 infusion are excluded.
Focus: The study evaluates the effectiveness of KTE-X19 therapy in treating patients who have achieved a partial response to Ibrutinib. Patients first continue Ibrutinib treatment, then receive preparation chemotherapy with cyclophosphamide and fludarabine, followed by the CAR-T cell therapy infusion. The study monitors response rates at 90, 180, and 365 days after infusion.
Investigational drugs: The main treatment is KTE-X19, a CAR-T cell therapy administered as an infusion. Ibrutinib is continued as oral 140 mg capsules. Preparation includes cyclophosphamide and fludarabine given through infusion before the CAR-T therapy.
Study on Loncastuximab Tesirine for Patients with Relapsed or Refractory Mantle Cell Lymphoma After Immunochemotherapy with Rituximab, Bendamustine, and Cytarabine
This study investigates loncastuximab tesirine as a consolidation therapy following a short course of combination immunochemotherapy (R-BAC) in patients who have previously been treated with or are intolerant to Bruton Tyrosine Kinase inhibitors.
Main inclusion criteria: Participants must be adults between 18 and 84 years old with confirmed mantle cell lymphoma diagnosis. They must have relapsed or refractory disease after one to four previous treatments and have received previous treatment with BTK inhibitors, either experiencing relapse/refractoriness or stopping due to side effects. They must be either new to bendamustine treatment or have relapsed at least one year after last bendamustine-containing treatment. Participants need measurable disease (at least 1.5 cm in longest diameter) and adequate organ function, including liver enzymes no more than 3 times normal, bilirubin no more than 1.5 times normal, and kidney function with creatinine clearance at least 40 mL/min. An ECOG performance status of 2 or less is required. Previous treatment with CAR-T or venetoclax is allowed.
Main exclusion criteria: Patients who have not been treated with BTK inhibitors or are not intolerant to them cannot participate. Those who have not experienced disease return or worsening after previous treatment, have not received 2 courses of R-BAC salvage immunochemotherapy, are outside the specified age range, or are part of vulnerable populations not selected for this study are excluded.
Focus: The study assesses how long patients can go without disease progression after receiving loncastuximab tesirine following R-BAC treatment. It evaluates overall survival, response rates, and safety. The treatment begins with two courses of R-BAC (rituximab, bendamustine, cytarabine) followed by consolidation with loncastuximab tesirine, all given intravenously. Regular monitoring and follow-up visits assess treatment response and detect any recurrence.
Investigational drugs: Loncastuximab tesirine is an antibody-drug conjugate administered intravenously. The initial treatment phase uses rituximab (targets specific cancer cell proteins), bendamustine hydrochloride (chemotherapy), and cytarabine (chemotherapy), all given intravenously.
Study of BGB-11417 for Patients with Relapsed or Refractory Mantle Cell Lymphoma
This study tests BGB-11417, a Bcl-2 inhibitor taken as a film-coated tablet, to evaluate its safety and effectiveness in treating mantle cell lymphoma that has returned or not responded to previous treatments.
Main inclusion criteria: Adult participants must have confirmed mantle cell lymphoma diagnosis and have received previous treatments including at least one targeting the CD20 protein and at least one Bruton Tyrosine Kinase Inhibitor. The disease must be relapsed or refractory and measurable. Tissue samples confirming the diagnosis must be available, or participants must be willing to have a new biopsy. An ECOG performance status of 0 to 2 is required, meaning participants should be capable of self-care. Adequate organ function is necessary. Both males and females can participate.
Main exclusion criteria: Patients with a different type of cancer, those currently receiving treatment for another cancer, those with severe or uncontrolled medical conditions, recent heart attack, severe heart problems, active infections requiring treatment, pregnant or breastfeeding women, participation in another clinical trial within the last 4 weeks, known allergies to the study drug, or major surgery within the last 4 weeks cannot participate. Those with a history of drug or alcohol abuse that could interfere with the study are also excluded.
Focus: The study is divided into two parts. Part one determines the safest and most effective dose through a ramp-up dosing schedule where the dose gradually increases. Part two assesses how well the treatment works at the recommended dose. Participants take BGB-11417 orally and undergo regular monitoring including blood tests, physical examinations, and possibly imaging tests. The study monitors response to treatment and side effects throughout.
Investigational drugs: BGB-11417 is a Bcl-2 inhibitor given as film-coated tablets taken orally. It works by blocking a protein that helps cancer cells survive, aiming to kill cancer cells or stop them from growing. Participants receive BGB-11417 alone without other cancer treatments.
Study of Brexucabtagene Autoleucel in Patients with Relapsed or Refractory Mantle Cell Lymphoma
This trial evaluates brexucabtagene autoleucel (KTE-X19), a cell therapy that modifies a patient’s own T cells to better recognize and attack cancer cells, in patients whose mantle cell lymphoma has returned or not responded to previous treatments.
Main inclusion criteria: Participants must be adults (18 years and older) with diagnosed relapsed or refractory mantle cell lymphoma. They must have received up to 5 previous treatments including chemotherapy with anthracycline or bendamustine and therapy with an anti-CD20 monoclonal antibody, but must not have received previous BTK inhibitor treatment. At least one measurable lesion is required. Participants need adequate blood counts (platelet count at least 75,000 per microliter), kidney function (creatinine clearance at least 60 cc/min), heart function (cardiac ejection fraction at least 50% with no fluid around the heart), and lung function (baseline oxygen saturation greater than 92% on room air). Both males and females are eligible.
Main exclusion criteria: Patients not diagnosed with relapsed or refractory mantle cell lymphoma, those outside the specified age range, those not part of the specified clinical trial groups, and those considered part of vulnerable populations cannot participate.
Focus: The study assesses the effectiveness of brexucabtagene autoleucel therapy. After initial assessment and confirmation of eligibility, participants receive pre-treatment medications (cyclophosphamide and fludarabine phosphate) through intravenous infusion to prepare the body. The main treatment involves receiving brexucabtagene autoleucel through intravenous infusion, closely monitored by healthcare professionals. Post-treatment monitoring includes regular follow-up visits with physical exams, blood tests, and imaging scans. Additional medications like tocilizumab and diphenhydramine hydrochloride may be provided to manage side effects. Long-term follow-up evaluates treatment effectiveness and monitors for late side effects over several months or years.
Investigational drugs: Brexucabtagene autoleucel (KTE-X19) is a CAR-T cell therapy using genetically modified immune cells to target and destroy cancer cells. It is administered as an infusion directly into the bloodstream. Preparation includes cyclophosphamide and fludarabine phosphate given intravenously.
Study of Ibrutinib and Rituximab for Patients with Relapsed or Refractory Mantle Cell Lymphoma
This study explores different treatment combinations for mantle cell lymphoma that has returned or not responded to previous therapies, comparing ibrutinib with rituximab versus other combination options including lenalidomide plus rituximab or bortezomib plus rituximab.
Main inclusion criteria: Adult patients must have confirmed mantle cell lymphoma with at least one previous treatment (but not with BTK inhibitors). They must have documented disease progression or relapse after their last treatment and measurable disease in the lymph nodes. An ECOG score of 0 or 1 is required, indicating full activity or ability to do light work. Adequate organ function is necessary, including white blood cells (ANC at least 1000 per mm3), platelets (at least 50,000 cells per mm3), hemoglobin (at least 8 g/dL), liver enzymes (no more than 3 times normal), bilirubin (no more than 1.5 times normal), and kidney function (creatinine clearance at least 30 mL/min). Patients must not have been diagnosed or treated for other cancers besides mantle cell lymphoma, with some exceptions. Females of childbearing potential and male participants with partners who can become pregnant must follow strict pregnancy prevention plans.
Main exclusion criteria: Patients without relapsed or refractory mantle cell lymphoma, those outside the adult age range, those unable to follow study procedures or take medication as required, those with other serious health conditions, pregnant or breastfeeding women, those participating in another clinical trial, those who had recent major surgery or are planning surgery during the study, and those with known allergies to the study medication cannot participate.
Focus: The study provides continued access to these treatment combinations for participants who benefit from them. Participants are randomly assigned to treatment groups and receive medications as capsules taken by mouth or as injections. Healthcare professionals closely monitor participants throughout the study to ensure safety and assess treatment effectiveness. The study continues until January 15, 2025, with participants receiving treatment as long as they continue to benefit.
Investigational drugs: Ibrutinib (140 mg hard capsules taken orally) blocks a specific protein that helps cancer cells grow and survive. Rituximab (500 mg concentrate for infusion) is an antibody therapy that targets protein on cancer cell surfaces. Lenalidomide (available in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg hard capsules) helps the immune system fight cancer. Bortezomib (3.5 mg solution for injection) interferes with cancer cell growth by blocking proteasomes.
Summary
The six ongoing clinical trials for refractory mantle cell lymphoma represent diverse treatment approaches across multiple European countries. Germany and Italy show notable concentration of trial activity, each hosting four and three trials respectively, while Belgium, Czechia, France, Netherlands, Poland, and Spain also participate in various studies.
The trials feature three main therapeutic approaches: CAR-T cell therapies (KTE-X19 and brexucabtagene autoleucel), novel targeted agents (BGB-16673, BGB-11417, loncastuximab tesirine), and combination therapies using established medications (ibrutinib, rituximab, lenalidomide, bortezomib). Two trials specifically focus on CAR-T cell therapy, representing an innovative immunotherapy approach that modifies patients’ own immune cells to fight cancer.
Most trials require participants to have received previous treatment with BTK inhibitors, reflecting the current standard of care. However, eligibility criteria vary regarding the number of previous treatments allowed, ranging from one to five prior therapies. The trials generally require adequate organ function and good performance status, with most setting an ECOG score of 0-2 as the threshold.
The concentration of BGB-11417 trials across six countries (Belgium, France, Germany, Italy, Poland, Spain) suggests significant interest in this Bcl-2 inhibitor as a potential treatment option. Similarly, the geographical spread of CAR-T cell therapy trials across France, Germany, Italy, Netherlands, and Spain indicates widespread evaluation of these innovative immunotherapies throughout Europe.
