In short
There are currently 2 clinical trials investigating new treatment approaches for mantle cell lymphoma stage III. These studies are testing combinations of targeted therapies, immunotherapies, and advanced CAR-T-cell treatments across multiple European countries.
Clinical trial locations
- Belgium
- Czechia
- Denmark
- Finland
- France
- Germany
- Italy
- Netherlands
- Norway
- Poland
- Portugal
- Spain
- Sweden
Study on CAR-T-cell Therapy with Rituximab and Ibrutinib for Patients with High-Risk Mantle Cell Lymphoma
This trial is exploring an innovative treatment approach using CAR-T-cell therapy for patients with high-risk mantle cell lymphoma who have not received prior treatment. CAR-T-cell therapy involves collecting and modifying a patient's own immune cells to better recognize and attack cancer cells.
Main inclusion criteria:
- Confirmed diagnosis of mantle cell lymphoma with specific genetic markers such as cyclin D1 overexpression or the t(11;14) genetic change
- Age between 18 and 75 years
- At least one measurable tumor or lesion
- Stage II-IV disease according to Ann Arbor staging
- At least one high-risk feature, such as a high MIPI-c score or TP53 genetic mutation
- No previous treatment for the condition
- Adequate organ function with specific laboratory values including neutrophils at least 1000 cells per microliter and platelets at least 75,000 cells per microliter
- Ability to reach the study site within 2 hours in case of emergency
Main exclusion criteria:
- Previous treatment for mantle cell lymphoma
- Not meeting high-risk criteria for the disease
- Outside the specified age range
- Belonging to vulnerable populations that may face additional risks
Trial focus: The study compares an experimental treatment approach combining rituximab, ibrutinib, and CAR-T-cell therapy (using KTE-X19, also known as brexucabtagene autoleucel or Tecartus) with standard treatment methods. Patients receiving the experimental treatment undergo abbreviated induction therapy with rituximab given through intravenous infusion and ibrutinib taken orally, followed by CAR-T-cell treatment, and then 6 months of ibrutinib maintenance therapy. The goal is to determine if this personalized immunotherapy approach can improve outcomes compared to current standard care.
Investigational drugs: The trial uses rituximab, a monoclonal antibody that targets specific proteins on cancer cell surfaces; ibrutinib, a kinase inhibitor that blocks proteins essential for cancer cell growth; and KTE-X19, a CAR-T-cell therapy that modifies the patient's own T-cells to target and destroy cancer cells more effectively.
Study on Ibrutinib and Drug Combination for Patients with Generalized Mantle Cell Lymphoma
This clinical trial is investigating different treatment strategies for patients with generalized mantle cell lymphoma. The study examines whether adding ibrutinib to standard chemotherapy, with or without stem cell transplantation, can improve treatment outcomes.
Main inclusion criteria:
- Confirmed diagnosis of mantle cell lymphoma according to WHO classification
- Age between 18 and 65 years
- Stage II-IV disease according to Ann Arbor staging
- No previous treatment for the condition
- At least one measurable tumor
- Suitable for high-dose treatment including high-dose Ara-C (cytarabine) chemotherapy
- ECOG/WHO performance status of 2 or less, meaning able to perform self-care activities
- Adequate laboratory values including neutrophil count at least 1000 cells, platelet count at least 100,000 cells, and appropriate liver and kidney function
- Agreement to use highly effective birth control methods during the study and for specified periods afterward
Main exclusion criteria:
- Any other type of cancer
- Previous cancer diagnosis unless treated with no recurrence for at least 5 years
- Serious heart problems or uncontrolled infections
- Pregnancy or breastfeeding
- Major surgery within the last 4 weeks
- Participation in another clinical trial
- Known allergies to the study drugs
- Severe liver or kidney disease
- History of drug or alcohol abuse
Trial focus: Participants are randomly assigned to one of three treatment groups. The control group receives standard R-CHOP/R-DHAP chemotherapy followed by autologous stem cell transplantation (ASCT). The two experimental groups receive R-CHOP with ibrutinib followed by R-DHAP, with one group then receiving ASCT plus ibrutinib maintenance, and the other group receiving only ibrutinib maintenance without transplantation. The study aims to compare failure-free survival, progression-free survival, and overall survival across these different treatment approaches.
Investigational drugs: The trial uses several treatment combinations including rituximab to target cancer cells, ibrutinib to interfere with cancer cell growth signals, Ara-C (cytarabine) chemotherapy to prevent cancer cell multiplication, R-CHOP and R-DHAP chemotherapy combinations that attack cancer cells in multiple ways, and ASCT (autologous stem cell transplantation), a procedure where healthy stem cells are collected from the patient and used to restore bone marrow after intensive chemotherapy.
Summary
Both ongoing trials for mantle cell lymphoma stage III focus on treatment approaches for patients who have not previously received therapy for their condition. A notable feature is the emphasis on ibrutinib, which appears as a key investigational drug in both studies, reflecting its importance in current treatment research for this type of lymphoma.
The trials are widely distributed across Europe, with the ibrutinib and drug combination study having the broadest reach, spanning 12 countries including Germany, Italy, Poland, Denmark, Sweden, Netherlands, Norway, Belgium, Finland, Portugal, Spain, and Czechia. The CAR-T-cell therapy study is conducted in 5 countries: Germany, France, Spain, Netherlands, and Czechia.
The studies represent two different treatment philosophies: one exploring personalized immunotherapy using modified immune cells (CAR-T-cell therapy), and the other comparing various intensities of chemotherapy with or without stem cell transplantation. Both trials include patients aged 18-65 or 18-75 years with stage II-IV disease, though they target slightly different risk profiles within this patient population.
