CHDM201K12201

Acute myeloid leukemia (AML) is a malignant, highly aggressive disease affecting a subgroup of white blood cells known as myeloid cells. An effective treatment for AML is allogeneic stem cell transplantation, which is often necessary. In this procedure, stem cells from a donor (e.g., a sibling) are transplanted; these cells settle in the bone marrow and form new, functional blood cells. Ideally, no leukemia cells should be detectable in the blood after treatment—this is called complete remission. However, some patients are at increased risk of the disease returning, for example, if the AML developed from a myelodysplastic syndrome. These patients require further therapy (maintenance therapy). The goal of the CHDM201K12201 study is to test the novel drug siremadlin—either alone or in combination with donor lymphocytes—following stem cell transplantation (SCT) for this situation. Siremadlin binds to the p53 protein, which is present in higher concentrations in tumor cells. This enhances the death of these cells. In therapy with donor lymphocytes (DLI), the patient is given immune cells (lymphocytes) from the stem cell donor. These cells trigger a renewed immune response against any leukemia cells that may still be present despite the stem cell transplant. This is intended to prevent a relapse of the disease. The study is divided into two phases. In the first phase, Siremadlin will be administered alone at various doses to determine the optimal dose (duration: up to 24 months). The second phase aims to evaluate the tolerability and effectiveness of the drug alone or in combination with donor lymphocytes. Of particular importance is whether the recurrence of leukemia can be prevented. Phase 2 is divided into three smaller phases: Initially, patients receive only siremadlin at the previously determined dose for at least two cycles (= 2 months). Subsequently, a combination of siremadlin and, if applicable, donor lymphocytes is administered for a maximum of three cycles. The treatment concludes with Siremadlin monotherapy. Phase 3 lasts a maximum of 2 years in total. The study is open-label and single-arm, meaning that every participating patient receives the therapy; there is no control group. Eligible participants are AML patients aged 18 and older who have undergone an allogeneic stem cell transplant and have no leukemia cells in their blood at the start of the study. They must have a “high-risk” profile.

Disease: Acute myeloid leukemia (AML) Cancer characteristics: An allogeneic stem cell transplant has been performed. The disease is currently inactive, but there is a “high-risk” profile for recurrence of disease activity What the study investigates: Evaluation of the dosage, tolerability, and effectiveness of siremadlin alone and in combination with donor lymphocytes (DLI) to prevent recurrence of AML Study objective: To evaluate the safety, tolerability, and dosing of siremadlin therapy (Phase 1), followed by an assessment of the efficacy of siremadlin therapy alone and in combination with DLI (Phase 2) How long will the study last: max. 4 years Study characteristics: 1 study arm, no blinding