Blinatumomab (drug) in addition to standard therapy for infants under 1 year of age with B-cell precursor acute lymphoblastic leukemia (ALL) (KMT2A mutation) or mixed-phenotype acute leukemia

B-cell precursor acute lymphoblastic leukemia (ALL) is a malignant disease of the blood-forming cells characterized by the uncontrolled production of malignant blasts in the bone marrow and blood. Blasts are immature forms of lymphocytes (white blood cells) that are part of the immune system. The overproduction of these abnormal blasts disrupts blood formation and the immune response. In ALL, other organs or the central nervous system may also be affected. Consequently, fatigue, anemia, blood clotting disorders, fever, and an increased susceptibility to infections may occur. The exact cause of ALL is not fully understood, but genetic mutations (such as the KMT2A mutation) play an important role, especially in infants, and influence the prognosis. If the affected cells exhibit characteristics of different cell subtypes, the condition is referred to as mixed-phenotype acute lymphoblastic leukemia (MPAL). This can influence the treatment regimen.

The standard treatment for ALL consists of intensive chemotherapy and, depending on the response and risk factors, a stem cell transplant if necessary. The goal is to achieve a complete cure of the disease. Treatment follows standardized treatment regimens (protocols), with the first phase of treatment referred to as induction. This is followed by the consolidation phase and then the maintenance phase. The study drug blinatumomab is a bispecific antibody that helps immune cells (T cells) recognize and destroy cancer cells (via the surface receptor CD19). At this time, blinatumomab is generally used for ALL only after first-line treatment has failed (relapse/refractory). It is already approved for this indication.

The goal of this Phase 3 study is to investigate the efficacy and safety of adding blinatumomab to standard chemotherapy as first-line therapy in infants with KMT2A-mutated ALL/MPAL. All patients will first receive standardized induction therapy. Risk stratification will then be performed based on the response to induction therapy and other prognostic factors. Patients are assigned to different risk groups accordingly, which influences their subsequent treatment (intermediate risk, high risk). All patients then receive one cycle of blinatumomab after completion of induction therapy. Intermediate-risk patients who respond well to the first cycle receive a second cycle of blinatumomab instead of a course of chemotherapy. Patients with an inadequate response are scheduled for an allogeneic hematopoietic stem cell transplant (HSCT). The study is open-label, meaning that medical staff and parents know which medications are being administered. Treatments and follow-up examinations as part of the study will continue for up to 8 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated.

Patients who are newly diagnosed with B-cell precursor acute lymphoblastic leukemia or mixed-phenotype acute leukemia (MPAL) within their first year of life (up to and including 365 days of age) are eligible to participate in this study. The disease must be untreated, and a KMT2A mutation (rearrangement) must be present.