Isatuximab as a New Treatment Option for Relapsed/Refractory CD38-Positive T-Cell ALL

Leukemias are malignant diseases of the white blood cells characterized by the uncontrolled growth of tumor cells. Acute lymphoblastic leukemia (ALL) is a rapidly progressing form of leukemia that affects so-called progenitor cells, from which white blood cells develop. T-cell ALL is a subtype of acute lymphoblastic leukemia and affects T cells, a subtype of white blood cells. Overall, it is significantly less common than the more frequent B-ALL. To date, there are fewer treatment options available for T-ALL. The malignant cells displace the healthy cells in the bone marrow that are responsible for blood formation. 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 mutations and infections may play a role. Treatment follows established treatment protocols that include various forms of chemotherapy. For some patients, a stem cell transplant is also required during the course of treatment. The primary goal is the complete elimination of leukemia cells, which can be measured in the blood, in the bone marrow, and using specialized molecular techniques. If there are signs of renewed disease activity or an inadequate response to therapy, further treatment options are necessary. Isatuximab is an antibody that targets the surface protein CD38, which may be present on T-ALL cells. This must be verified beforehand. If CD38 is found on the surface of the cancer cells, isatuximab can recognize and destroy them. This medication is already approved for the treatment of multiple myeloma, another form of blood cancer in which CD38 is regularly present on the affected cells. It has not yet been approved for T-ALL.

The goal of this study is to further investigate this novel therapeutic approach. All patients participating in the study will receive the drug. All study participants must have a recurrence of the disease or be refractory to previous standard therapy. Which group within the study patients are then treated in depends on how much time has passed since their first therapy and how advanced the disease is upon recurrence. The first group includes adults in whom the disease has not completely gone into remission despite chemotherapy or has relapsed—for example, shortly after the initial treatment, following a stem cell transplant, or when salvage therapy has failed. The second group includes patients who, although they no longer have visible cancer cells in their blood or bone marrow after chemotherapy, still have minimal traces of leukemia cells detectable in the laboratory (known as MRD, minimal residual disease). The study aims to determine whether isatuximab can help reduce the risk of relapse and improve treatment outcomes in both situations. Since assignment to one of the two groups is predetermined, there is no random assignment, and both the patient and the treating physicians know which group the treatment is being administered in. In Group 1, isatuximab is administered in combination with standard therapy; in Group 2, isatuximab is administered alone, without additional therapy. The effectiveness of the treatment will be evaluated after approximately 9 weeks. Overall, follow-up will continue for approximately 18 months.

Women and men aged 18 and older with CD38-positive T-cell ALL are eligible to participate in the study. The disease must be relapsed/refractory following treatment, or classified as “molecular failure” or “molecular relapse.” In addition, patients must have recovered from previous chemotherapy and meet specific criteria for liver and kidney function.