Comparison of Two Chemotherapy Regimens Prior to Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) (RELEVANT Study)

In acute myeloid leukemia (AML), immature white blood cells (blasts) multiply uncontrollably in the bone marrow and suppress normal blood cell production. Myelodysplastic syndrome (MDS) is also a bone marrow disorder in which blood production is impaired and which can progress to AML. In both conditions, an allogeneic stem cell transplant can lead to a cure. In this procedure, stem cells from a donor are transplanted. Prior to the transplant, patients receive what is known as conditioning chemotherapy as a preparatory treatment, which destroys the diseased bone marrow and makes room for the new stem cells. Established combination therapies include treosulfan plus fludarabine and melphalan plus fludarabine.

The aim of this Phase 2 study is to compare the two pre-treatment regimens in terms of their efficacy and tolerability. To this end, patients will be randomly assigned to two groups. Group 1 will receive treosulfan (from Day 4 to Day 2 before the stem cell transplant) along with fludarabine (from Day 6 to Day 2 before the stem cell transplant). Group 2 will receive a single dose of melphalan (on Day 2 before the stem cell transplant) together with fludarabine (from Day 6 to Day 2 before the stem cell transplant). All medications will be administered as intravenous infusions. The study is open-label (not blinded). This means that both the study team and the patients know which treatment is being administered. After the transplant, all patients will receive preventive treatment against graft-versus-host disease (GvHD) with the already approved chemotherapeutic agent and immunosuppressant cyclophosphamide. In GvHD, the donated immune cells attack the recipient’s body; the goal is to alleviate this by suppressing the immune system. The main objective (the primary endpoint) of the study is overall survival two years after transplantation. Additional objectives include, among others, the relapse rate, relapse-free survival, and the occurrence of GvHD.

Women and men aged 18 and older with AML in remission (remission of the disease) or MDS who are scheduled to undergo an allogeneic stem cell transplant within the next three weeks are eligible to participate in this study. A prerequisite is an increased risk of treatment-related side effects. This may include being 50 years of age or older, having certain comorbidities, or being scheduled for a second allogeneic transplant.