Golden Gate Study

Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoietic system characterized by the uncontrolled production of blasts in the bone marrow and blood. Blasts are a precursor form of white blood cells, which are part of the body’s immune system. Depending on the type of blood cells affected, the condition is classified as B-cell ALL or T-cell ALL. The overproduction of abnormal blasts disrupts blood formation and the immune system. Consequently, fatigue, anemia, blood clotting disorders, fever, and an increased susceptibility to infections may occur. More than half of patients have swollen lymph nodes and an enlarged spleen. The exact cause of ALL is not fully understood, but genetic mutations and environmental factors play a role. For example, errors in cell division can cause parts of one chromosome to be transferred to another. In these patients, the condition is referred to as Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The standard treatment for ALL is divided into several phases: pre-treatment, induction, consolidation, and maintenance therapy. The goal of induction therapy is to achieve complete remission of the disease. In the subsequent phases of therapy, this effect is to be maintained with the goal of a complete cure. This therapy is based on various chemotherapeutic agents and is, overall, very intensive and associated with a correspondingly high incidence of side effects.

The goal of this Phase 3 study is to investigate the efficacy and safety of treatment with blinatumomab and a lower-dose chemotherapy regimen in a larger number of patients. Blinatumomab is a so-called bispecific antibody that binds simultaneously to cancer cells and the body’s own immune cells, thereby helping the immune system to recognize and destroy the cancer cells. The drug is already approved for the treatment of relapsed or refractory Ph-negative B-precursor ALL. This form of therapy will be compared with the current standard of care. Participants will be randomly assigned to one of the two groups as part of the study. Before randomization, a safety run with blinatumomab and low-dose chemotherapy will first be conducted to identify any potential side effects of the therapy. Subsequently, Group 1 will receive the combination of blinatumomab and low-dose chemotherapy. Group 2 will receive chemotherapy according to the standard treatment protocol (GMALL or HyperCVAD). The study is open-label, meaning that both the medical staff and the patients know which medications are being administered. Treatments and follow-up visits as part of the study will continue for up to 5 years, during which the effectiveness 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 treatment. The primary endpoints of the study are overall survival and event-free survival.

Patients aged 55 or older, or 40 or older with severe comorbidities, who have B-precursor ALL are eligible to participate in the study. The disease must be newly diagnosed and Ph-negative.

Facts:

Disease: B-cell precursor acute lymphoblastic leukemia (B-precursor ALL)

Cancer characteristics: Philadelphia-negative, newly diagnosed

What the study investigates: Efficacy and safety of blinatumomab + low-dose chemotherapy compared to standard therapy (without blinatumomab)

Study objective: To improve treatment options and survival rates

Study duration: Approximately 5 years

Study characteristics: Two treatment arms, randomized, open-label, Phase 3