VIALE-T

Acute leukemias are malignant diseases of white blood cells (leukocytes) that are classified into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), depending on the specific subtypes of leukocytes affected, and each requires targeted therapies. Treatment for AML is generally based on the patient’s condition and the characteristics of the disease, which can vary from patient to patient. Treatment generally follows this regimen: First, chemotherapy is used to attempt to completely eliminate the disease (induction therapy). The goal is then to stabilize this leukemia-free state; in many cases, an allogeneic stem cell transplant is used for this purpose (consolidation). In this procedure, so-called stem cells from a unrelated donor (e.g., a sibling) are administered; these cells settle in the bone marrow and form new, functional blood cells. The third part of the treatment is divided into patients who do not require further therapy and those who require maintenance therapy. In cases with an unfavorable prognosis and no chance of a cure, the focus is on quality of life; in such cases, no AML-specific therapy is administered (best supportive care). Venetoclax has been tested in the treatment of AML for several years but is not yet considered a standard medication. It binds to a protein in the body, thereby triggering the death of tumor cells. Azacitidine, a chemotherapy drug, is already used to treat AML patients for whom an allogeneic stem cell transplant is not an option. Azacitidine is incorporated into the DNA of cancer cells but has a different structure, thereby halting the growth of these cells. Both drugs are already in use, and safety data are available. The goal of the study is to test the use of venetoclax in combination with azacitidine in AML patients following an allogeneic stem cell transplant. The initial phase (Phase 1, 1 month) will determine the optimal dosage (tolerability). In Phase 2 (starting in the 2nd month), based on the dose determined in Phase 1, the study will test whether long-term therapy with venetoclax and azacitidine (max. 24 cycles of 28 days each, approx. 2 years) is superior to therapy focused solely on quality of life—specifically, whether patients live longer with this regimen. Azacitidine will be administered for only 6 cycles; thereafter, only venetoclax will be given. The key questions are therefore: what is the overall survival time after the start of therapy (Phase 2), the time without recurrence of leukemia (Phase 2), and the incidence of side effects (Phase 1)? A prerequisite for participation is planned or previously completed allogeneic stem cell therapy. For the first phase, participants must be at least 18 years old; the minimum age for the second phase is 12 years.

Facts:  Disease: acute myeloid leukemia (AML)  Cancer characteristics: prior treatment with allogeneic stem cell therapy (SCT)  What the study investigates: safety and efficacy of the combination of venetoclax and azacitidine compared to measures focused solely on quality of life  Study objective: to investigate the dose tolerance of venetoclax and azacitidine (Phase 1). Overall survival compared to measures focused solely on quality of life (Phase 2)  Study duration: approx. 2 years  Study characteristics: 2 study arms (starting in Phase 2), random assignment, open-label (assignment known), 2 phases (Phase 1: dose-finding, Phase 2: efficacy)