A new CAR-T cell therapy for previously treated leukemias (ALL, CLL) and B-cell non-Hodgkin lymphomas in children and adults

Leukemias and B-cell non-Hodgkin lymphomas (NHL) are malignant diseases of the blood and lymphatic system characterized by the uncontrolled growth of tumor cells. The causes of these diseases are often not fully understood, but genetic factors and environmental factors may play a role. Leukemias are characterized by the uncontrolled growth of white blood cells in the blood. In lymphomas, these abnormal lymphocytes are often first detected in the lymph nodes. Symptoms vary depending on the specific disease. They may include swollen lymph nodes, an enlarged spleen, fatigue, increased susceptibility to infections, fever, an increased tendency to bleed, weight loss, and night sweats. Some symptoms result from the fact that more and more healthy blood cells are being displaced by the cancer cells. First-line treatment depends on the type of disease, the age, and the physical condition of the affected patients. Treatment may include chemotherapy, immunotherapy, radiation therapy, or a stem cell transplant, and multiple forms of therapy may be combined. Despite these treatments, the disease may return (recur) in some patients or fail to respond to therapy (become refractory), so new drugs are being sought for these situations.

One novel treatment method is CAR-T cell therapy. This involves the patient’s own immune cells (T cells), which are harvested from the patient and genetically modified so that they can specifically recognize and destroy cancer cells. In this form, they are reinfused into the patient as a single infusion. The CAR-T cells in this study (MB-CART19.1) recognize the CD19 surface marker on B cells (lymphocytes). This Phase 1/2 study is testing the novel CAR-T cell therapy MB-CART19.1. The study consists of two phases: In Phase 1 (dose escalation), the optimal dose of MB-CART19.1 will be determined across three study groups. Three patients in each group will receive a predetermined dose of MB-CART19.1 as an infusion. The remaining patients will then receive a higher dose until the optimal dose is found, which is determined primarily by tolerability. Subsequently, in Phase 2 (dose expansion), the safety, tolerability, pharmacokinetics (how the body absorbs, distributes, metabolizes, and excretes the drug), and efficacy of the optimal dose identified in Phase 1 will be evaluated in a larger group. The study is open-label (i.e., neither the medical staff nor the patient is blinded to which medication is being administered). The examinations and follow-up visits as part of the study will take place over a period of up to 5 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. A key factor is whether or when the disease progresses again during therapy. Patients with CLL, ALL, or B-cell non-Hodgkin lymphoma can participate in this study starting at age 2. The disease must have been previously treated and must either be refractory or have relapsed. The cells must express the surface marker CD19, which is typical for the diseases described.