Ongoing Clinical Trials for Mantle Cell Lymphoma Stage IV
There are currently 2 ongoing clinical trials investigating new treatment approaches for mantle cell lymphoma stage IV. These trials are testing innovative therapies including CAR-T-cell therapy combined with targeted medications and examining different treatment sequences with and without stem cell transplantation. The trials are being conducted across multiple European countries and are open to patients who meet specific health criteria.
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 for patients with high-risk mantle cell lymphoma who have not yet received any treatment for their condition. The study compares a new experimental strategy using CAR-T-cell therapy with the current standard treatment methods.
Main inclusion criteria: Patients eligible for this trial must be between 18 and 75 years old with a confirmed diagnosis of mantle cell lymphoma, including specific markers like overexpression of cyclin D1 or presence of a genetic change called t(11;14). They must have at least one measurable tumor or lesion, and their disease must be at stage II-IV. Participants need to have reasonable overall health, with an ECOG performance status of 2 or less, meaning they can carry out self-care but may not be able to work. Laboratory tests must show adequate blood cell counts and organ function. The disease must not have spread to the central nervous system, and patients must have at least one high-risk feature, such as a high score on a specific risk index or a genetic mutation called TP53. Participants must be able to reach the study site within 2 hours in case of emergency and agree not to drive for 8 weeks after receiving CAR-T-cell treatment.
Main exclusion criteria: Patients who have already received any treatment for mantle cell lymphoma cannot participate. Those who are not considered high-risk, meaning their disease is less likely to progress quickly, are also excluded. Patients outside the specified age range or who belong to vulnerable populations may not be eligible. Other specific health criteria must also be met to ensure the safety and appropriateness of participation.
Trial focus: The study involves dividing participants into two groups. One group receives the experimental treatment, which includes a combination of rituximab and ibrutinib followed by CAR-T-cell therapy using a medication called KTE-X19 (brexucabtagene autoleucel, marketed as Tecartus). This therapy involves modifying the patient’s own immune cells to better target cancer cells. Following the CAR-T-cell treatment, patients continue with ibrutinib maintenance therapy for 6 months. The other group receives standard treatment, which typically includes various chemotherapy combinations. Throughout the trial, patients are closely monitored through regular check-ups and tests to assess their response to treatment and overall health.
Investigational drugs: The trial uses three main treatments. Rituximab is given through intravenous infusion and helps the immune system destroy cancer cells by targeting specific proteins on their surface. Ibrutinib is taken orally as a capsule and works by interfering with the pathways that cancer cells use to grow and survive. It is used both during initial treatment and as maintenance therapy. KTE-X19 is a specialized CAR-T-cell therapy given through infusion that involves modifying a patient’s own immune cells to better recognize and attack cancer cells, offering a personalized treatment approach.
Study on Ibrutinib and Drug Combination for Patients with Generalized Mantle Cell Lymphoma
This trial is investigating different treatment strategies for patients with generalized mantle cell lymphoma. The study aims to determine the best treatment approach by comparing three different combinations of therapies.
Main inclusion criteria: Eligible patients must be between 18 and 65 years old with a confirmed diagnosis of mantle cell lymphoma according to WHO classification. The disease must be at stage II-IV according to the Ann Arbor staging system, and patients must not have received any previous treatment. Participants must have at least one measurable tumor, though if the cancer is only present in the bone marrow, specific bone marrow tests are required. They need to be suitable for high-dose treatment, including high-dose Ara-C chemotherapy, and have an ECOG/WHO performance status of 2 or less. Laboratory tests must show adequate blood cell counts and organ function, including neutrophil counts of at least 1000 cells, platelet counts of at least 100,000 cells, and acceptable liver and kidney function. Men and women who can have children must agree to use highly effective birth control methods during the study and for specific periods after treatment ends.
Main exclusion criteria: Patients with any other type of cancer apart from generalized mantle cell lymphoma are excluded, unless a previous cancer was treated and has not returned for at least 5 years. Those with serious heart problems, uncontrolled infections, severe liver or kidney disease, or a history of drug or alcohol abuse cannot participate. Pregnant or breastfeeding women are excluded, as are patients who have had major surgery within the last 4 weeks. Those currently participating in another clinical trial or with known allergies to the study drugs are also not eligible.
Trial focus: Participants are randomly assigned to one of three treatment groups. The control group receives standard treatment with R-CHOP chemotherapy followed by R-DHAP and an autologous stem cell transplant (ASCT). The first experimental group receives R-CHOP with ibrutinib, followed by R-DHAP, ASCT, and maintenance therapy with ibrutinib. The second experimental group receives R-CHOP with ibrutinib, followed by R-DHAP and maintenance therapy with ibrutinib, but without the stem cell transplant. The study monitors participants through regular follow-up assessments, including physical exams, laboratory tests, and imaging studies, to evaluate how long they remain free from disease progression and to assess overall survival rates.
Investigational drugs: The trial uses several medications and procedures. Rituximab targets specific cells in the immune system involved in cancer growth. Ibrutinib, taken orally, interferes with signals that cancer cells need to grow and divide. Ara-C (cytarabine) is a chemotherapy drug that prevents cancer cells from growing and multiplying by interfering with their DNA. R-CHOP and R-DHAP are combinations of different chemotherapy drugs that work together to attack cancer cells in multiple ways. ASCT (autologous stem cell transplantation) is a procedure where healthy stem cells are collected from the patient’s own body and used to replace damaged bone marrow after intensive chemotherapy, helping the body recover and produce healthy blood cells.
Summary
Both ongoing trials for stage IV mantle cell lymphoma are exploring innovative treatment approaches for patients who have not yet received therapy for their condition. The trials share a common focus on incorporating ibrutinib, a targeted therapy that blocks specific proteins helping cancer cells grow, into treatment regimens.
Geographically, these trials show a strong presence across Europe, with Germany, Spain, Netherlands, and Czechia participating in both studies. The second trial has broader geographic reach, spanning 12 countries including Scandinavian nations (Denmark, Sweden, Norway, Finland) and several Central and Southern European countries.
The first trial is particularly notable for its investigation of CAR-T-cell therapy (KTE-X19), a personalized immunotherapy approach that modifies patients’ own immune cells to fight cancer. This represents a cutting-edge treatment strategy being compared against standard care. The second trial takes a different approach, comparing three treatment strategies that vary in their use of stem cell transplantation, allowing researchers to determine whether this intensive procedure provides additional benefits when combined with targeted therapy.
Both studies are designed for patients with high-risk features and require participants to meet specific health criteria to ensure their safety during treatment. The trials will help determine which treatment strategies provide the best outcomes for patients with this challenging form of lymphoma.
