Phase 1/2 Trial of Rapcabtagen Autoleucel (CAR-T cell therapy) for Leukemias and Lymphomas

Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), acute lymphoblastic leukemia (ALL), and large B-cell lymphoma (LBCL) are malignant diseases of the hematopoietic system. CLL, SLL, DLBCL, and LBCL are types of non-Hodgkin lymphoma and affect B lymphocytes, a subtype of white blood cells that are part of the immune system. ALL is a rapidly progressing form of leukemia and affects so-called progenitor cells, from which blood cells develop. Possible symptoms include swollen lymph nodes, an enlarged spleen, fatigue, increased susceptibility to infections, fever, an increased tendency to bleed, night sweats, and weight loss. The exact causes of these diseases are not fully understood, but genetic factors and environmental factors may play a role. Standard treatments for these diseases include chemotherapy, immunotherapy, and, in some cases, stem cell transplantation.

A new form of therapy is treatment with CAR-T cells, which has already shown good results for some diseases and has been approved. In this process, the patient’s own immune cells (T cells) are harvested and genetically modified so that they can specifically recognize and destroy cancer cells. They are then reinfused into the patients. A new, as yet unapproved CAR-T cell drug is Rapcabtagen Autoleucel, which is already being used in the United States in certain situations.

The goal of this study is first to determine the optimal dose of Rapcabtagen Autoleucel therapy (Phase 1) and then, in Phase 2, to further investigate the efficacy and safety of the therapy in a larger, selected group of patients. The study does not involve random assignment to treatment groups (non-randomized), and it is open-label (unblinded), meaning that both medical staff and patients know which treatment is being administered.

In Phase 1 (dose-finding, already completed), patients with DLBCL, LBCL, and ALL received Rapcabtagen Autoleucel alone. The drug was administered as a single dose. The dose was gradually increased in different patients to determine the optimal dose. In Phase 1, SLL and CLL patients received a combination of Rapcabtagen Autoleucel and ibrutinib, a tyrosine kinase inhibitor. This medication is already an established standard of care and is approved.

In the extended Phase 2 (dose-expansion phase, currently ongoing), treatment with Rapcabtagen Autoleucel is being administered to patients with DLBCL and LBCL. The study will follow patients for up to 2.5 years after a single CAR-T cell infusion, during which the efficacy of the therapy and the occurrence of side effects from the drug will be evaluated. A key factor is whether or when the disease progresses again during therapy. Phase 1 primarily investigates the occurrence of dose-limiting side effects, while Phase 2 examines the rate of complete response to the therapy.

Patients aged 18 and older with CLL, SLL, DLBCL, ALL, or LBCL are generally eligible to participate in this study (depending on the phase). For LBCL (at least 1 prior therapy) and DLBCL (at least 2 prior therapies, including one anti-CD20 therapy and anthracycline), the disease must have been previously treated and must now be progressing again (relapsed/refractory). No prior therapy targeting the B-cell surface marker CD19 may have been administered. Patient enrollment for the Phase 1 study has already been completed. The Phase 2 study is currently recruiting only for DLBCL and LBCL.