Treatment with blinatumomab, a tyrosine kinase inhibitor, and chemotherapy for newly diagnosed B-cell acute lymphoblastic leukemia in children, adolescents, and young adults

B-ALL originates in the bone marrow. There, immature precursor cells of B lymphocytes—which are a type of white blood cell—undergo genetic changes. They stop maturing, multiply rapidly, and increasingly displace normal blood cell production. In Philadelphia chromosome-positive B-ALL, the BCR and ABL1 genes are fused together (BCR::ABL1), resulting in a persistently active protein from the tyrosine kinase family that continuously signals the cells to proliferate and survive. In Ph-like B-ALL with an ABL-class gene fusion, genes such as ABL1, ABL2, CSF1R, or PDGFRB are rearranged instead, which can also result in a constantly active growth signal. Dasatinib and imatinib belong to the class of tyrosine kinase inhibitors; they are designed to inhibit such persistently active proteins and are taken as tablets. Blinatumomab is a bispecific antibody that binds with one end to the CD19 protein on the surface of leukemia cells and with the other end to the body’s own immune cells, the T cells, thereby bringing the two into close contact. It is administered as an intravenous infusion.

The aim of this Phase 2 study is to evaluate a treatment regimen in which three cycles of blinatumomab are incorporated into a modified standard chemotherapy regimen and consistently combined with a tyrosine kinase inhibitor, while omitting the usual consolidation chemotherapy. The main objectives (primary endpoints) are event-free survival (EFS) at three years, as well as the safety and tolerability of this treatment. An additional objective is overall survival (OS) at three years. All patients will receive the study treatment; there is no control group. Assignment to the three parallel treatment groups is not random (non-randomized) and is based on the genetic alteration of the leukemia cells: Stratum 1 for Ph+ B-ALL (dasatinib), Stratum 2 for an ABL-class gene fusion with PDGFRB (imatinib), and Stratum 3 for such a fusion without PDGFRB (dasatinib). The study is open-label, meaning that both the patients and the study physicians know which treatment is being administered. Treatment lasts for approximately two years from the start of induction therapy. In addition, medications are administered into the cerebrospinal fluid—the fluid surrounding the brain and spinal cord—to prevent or treat involvement of the nervous system. During the course of the study, blood, cerebrospinal fluid, and bone marrow samples will be collected, and heart function will be monitored.

Patients between the ages of one and under 46 whose leukemia cells express CD19 are eligible to participate. Induction therapy must have already begun or been completed, and a tyrosine kinase inhibitor may have been administered only for a short time prior to enrollment. Patients who are ineligible include, among others, those with a history of chronic myeloid leukemia or leukemia resulting from prior cancer treatment.