Study on the Safety and Dose-Finding of a New CAR-T Cell Therapy in Children and Adults with Recurrent or Treatment-Resistant B-Cell Diseases

B-cell malignancies encompass various malignant diseases of the lymphatic system. In these diseases, certain white blood cells multiply uncontrollably. These blood cells are called B lymphocytes. This group of diseases includes lymphomas. These include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma. Chronic lymphocytic leukemia (CLL), despite its name, is also classified as a B-cell lymphoma. Leukemias can also arise from the precursors of B-lymphocytes, such as acute lymphoblastic leukemia (ALL). The standard treatment is usually chemotherapy combined with targeted antibody therapies. Despite intensive treatment, some patients experience a relapse or the disease does not respond adequately to therapy. In such cases, CAR-T cell therapies are increasingly being used. CAR-T cell therapies are a form of immunotherapy in which the body’s own immune cells (T cells) are extracted from the blood and genetically modified in the laboratory. The cells are then returned to the body via a intravenous infusion. These modified cells recognize specific surface markers on the cancer cells—such as CD19—and can now destroy them in a targeted manner. However, cancer cells can lose the CD19 target marker over time. In this case, the therapy becomes less effective because the CAR-T cells can no longer reliably recognize the tumor cells. The study drug MB-CART2219.1 is an advanced CAR-T cell therapy that targets two surface markers simultaneously: CD19 and CD22. This is intended to prevent cancer cells from evading treatment by losing a single target marker. This dual-target CAR-T cell therapy is not yet approved.

The primary goal of the Phase 1 trial is to assess the safety and feasibility of MB-CART2219.1 and to determine the appropriate dosage. The study is single-arm, meaning that all patients will receive MB-CART2219.1, but different dose levels will be tested. The study will begin with a low dose and gradually increase it. The study follows a 3+3 design. The 3+3 design is a classic method used in Phase 1 trials to determine the maximum tolerated dose (MTD) in cancer research. First, three patients receive a dose. If they tolerate the dose well, three additional patients are treated with the next higher dose. In this way, the dose is increased step by step. The goal is to find a dose that is effective and causes as few side effects as possible. The study is open-label, meaning that both medical staff and patients know which treatment is being administered. The study consists of two groups. Group 1 includes adults aged 18 and older with lymphoma. Group 2 includes children and adolescents aged 12 and older with ALL. The primary goal of the study is to assess the safety of this new CAR-T cell therapy. Patients will be followed for a total of 6 months. After that, long-term follow-up of up to 15 years is planned.

Children aged 12 and older with ALL and adults up to age 75 with lymphoma are eligible to participate. They must have a recurrent or hard-to-treat B-cell malignancy. A prerequisite is that the cancer cells express CD19 or CD22. In addition, patients must have received at least two prior systemic treatments, including an approved CAR-T cell therapy or a so-called bispecific antibody. For CLL, prior treatment with a specific targeted therapy (BTK inhibitors) must have been completed. Patients who have experienced a relapse following a stem cell transplant are also eligible to participate. Pregnant and breastfeeding women are not eligible to participate in the study.