New CAR-T cell therapy for previously treated patients with ALL (children and adults) and various types of non-Hodgkin lymphoma

Acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) are malignant diseases of the blood and lymphatic system characterized by the uncontrolled growth of immune cells. The causes of these diseases are often not fully understood, but genetic factors and environmental factors play a role. ALL is characterized by the uncontrolled growth of precursor cells of white blood cells (lymphoblasts). In non-Hodgkin lymphomas, more mature lymphocytes (also a type of white blood cell) are affected. NHL encompasses an entire group of diseases that differ in their specific manifestations. The present study includes the following NHLs: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL). Many of these diseases (ALL, DLBCL, FL, MCL, CLL) originate in B-lymphocytes, which often express the CD19 protein on their surface. This can be an important target for specific therapy. Symptoms vary depending on the 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 cancer cells are displacing an increasing number of healthy blood cells. Initial treatment depends on the type of disease, the patient’s age, and their overall physical condition. Treatment may include chemotherapy, immunotherapy, radiation therapy, or a stem cell transplant—often in combination. Despite these treatments, the disease may return (recur) in some patients or fail to respond to therapy (refractory), leading to a poor prognosis. In such cases, CAR-T cell therapy may be an option. CAR-T cells are the body’s own immune cells (T cells) that are harvested from the patient and genetically engineered to specifically recognize and destroy cancer cells when they are reinfused into the patient. Administration is usually a one-time procedure.

The goal of this Phase 1/2 study is to investigate the efficacy, safety, and optimal dose of a new CAR-T cell therapy that specifically targets the CD19 surface marker on cancer cells. As part of the study, all patients will receive the CAR-T cell therapy. First, patients will undergo pretreatment with fludarabine and cyclophosphamide (chemotherapy) over 3 days to temporarily suppress the immune system (lymphodepleting chemotherapy). The CAR-T cells are then administered as a single infusion. In Phase 1 of the study, the dose of the medication will be gradually increased in different participants to determine the maximum tolerated dose. The study is open-label, meaning that both the medical staff and the patient know which treatment is being administered. The examinations and follow-up visits as part of the study will continue for up to 15 years after the infusion, with the most intensive monitoring taking place during the first few months. The study will evaluate the therapy’s efficacy and the occurrence of side effects. In addition, the feasibility of isolating and processing CAR-T cells prior to treatment in a clinical setting is being evaluated. The primary endpoint of the study is the occurrence of treatment-related dose-limiting adverse events in Phase 1 and response in Phase 2.

Patients aged 18 and older with CD19-positive ALL, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL) are eligible to participate in this study. Children and adolescents between the ages of 3 and 18 with ALL may also participate in the study and will be evaluated as a separate group. The disease must have been previously treated and must either be uncontrollable (refractory) or show signs of a recurrence.