Clinical Research Directory

Observational Study on Eltrombopag in Hypocellular Myelodysplastic Neoplasms

Hypocellular myelodysplastic neoplasms (h-MDS) are a distinct entity introduced in the 2022 WHO classification. They are characterized by reduced bone marrow cellularity and may share several clinical, morphological, immunological, and molecular features with aplastic anemia (AA), making the differential diagnosis between the two conditions challenging. Eltrombopag, a thrombopoietin receptor agonist, has demonstrated efficacy in patients with severe AA and has also shown activity in lower-risk MDS, with bone marrow hypocellularity identified as a potential predictor of response. In Italy, eltrombopag has been used off-label in patients with h-MDS and clinically relevant cytopenias. However, systematic real-world data on its effectiveness and safety in this patient population, either as monotherapy or in combination with immunosuppressive therapy (IST), remain limited. This is an observational study. We plan to analyse all patients with h-MDS consecutively diagnosed and included in the FISIM registry in 26 Italian centres. Study duration: 12 months Data to be collected: demographic, disease characteristics at diagnosis (blood count, morphology, histopathology, cytogenetics, multiparameter flow cytometry, presence of PNH clone, molecular data), response to treatment according to IWG criteria, progression to AML rate and survival. Centralized revision of bone marrow biopsy: bone marrow biopsy at diagnosis will be centrally reviewed

Proton-Based Total Marrow Irradiation for Allogeneic Transplantation in High-Risk AML/MDS

This is an open-label, single-center, non-randomized phase I/II pilot study evaluating proton-based Total Marrow Irradiation (TMI) as part of the conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients with high-risk or relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). These patients have an unfavorable prognosis with standard conditioning approaches. Participants will receive a standard conditioning regimen consisting of either myeloablative or reduced-intensity chemotherapy, selected according to age and comorbidities, combined with proton TMI delivered at a total dose of 12 Gy in three fractions. Graft-versus-host disease (GvHD) prophylaxis will be administered according to institutional standards, preferentially using post-transplant cyclophosphamide. Patients will subsequently undergo standard allo-HSCT and will be followed for at least 24 months after transplantation. The primary objective of the study is to assess the safety and tolerability of proton TMI added to standard conditioning, as measured by non-relapse mortality and treatment-related toxicity within the first 100 days after transplantation. Secondary objectives include evaluation of engraftment kinetics, incidence of relapse, overall and relapse-free survival, GvHD outcomes, and quality of life. Study outcomes will be analyzed descriptively and compared with a matched historical cohort.

Oral-ATO for TP53-mutated Myeloid Malignancies

This is an open-label, phase 2 study of oral arsenic trioxide (Arsenol ®) in combination with ascorbic acid and investigator choice of low-intensity therapy in patients with previously untreated or relapse/refractory TP53-mutated acute myeloid leukemia (AML), myelodysplastic neoplasm (MDS), chronic myelomonocytic leukemia (CMML).

Repurposing Metformin As a Leukemia-preventive Drug in CCUS and LR-MDS

This is a single-arm pilot study of the feasibility and safety of metformin in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic neoplasms (LR-MDS).

Intensive Conditioning withTHI/Bu/Flu/Ara-C in Allo-HSCT for Myeloid Malignancies With Extramedullary Involvement

This study is a multicenter, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an intensive conditioning regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of myeloid malignancies with extramedullary involvement. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d from d -9 to d -8 (2 days), fludarabine at 30mg/m2/d from d -7 to d -3 (5 days), cytarabine at 1-1.5g/m2/d from d -7 to d -3 (5 days), and busulfan at 3.2mg/kg/d from d -5 to d -3 (3 days). Conditioning begins on day -9, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.