Efficacy and Safety of UCBT With TMI -Based Conditioning Regimen for Adults With Refractory/Relapsed Aplastic Anemia

Trial details

Who runs it

Institute of Hematology & Blood Diseases Hospital, China

Trial code

NCT07078721

Record updated

22 July 2025

Original description

Refractory/relapsed aplastic anemia (AA) in adults remains a clinical challenge that is frequently encountered and urgently needs to be resolved. Salvage treatment should prioritize hematopoietic stem cell transplantation (HSCT). Unrelated cord blood is an ideal source of hematopoietic stem cells due to its easy availability, low immunogenicity, and low incidence of chronic graft-versus-host disease (cGVHD) after transplantation.The optimization of the conditioning regimen for UCBT is a crucial factor in determining patient outcomes.Read full original descriptionShow less

Efficacy and Safety Study of Umbilical Cord Blood Transplantation (UCBT) With Total Marrow Irradiation (TMI)-Based Conditioning Regimen for Adults With Refractory/Relapsed Aplastic Anemia (AA).

Refractory/relapsed aplastic anemia (AA) in adults remains a clinical challenge that is frequently encountered and urgently needs to be resolved. Salvage treatment should prioritize hematopoietic stem cell transplantation (HSCT). Unrelated cord blood is an ideal source of hematopoietic stem cells due to its easy availability, low immunogenicity, and low incidence of chronic graft-versus-host disease (cGVHD) after transplantation.The optimization of the conditioning regimen for UCBT is a crucial factor in determining patient outcomes.

This is a Phase II clinical study. A total of 11 adult patients with refractory/relapsed AA will be treated with a UCBT regimen based on a TMI-based conditioning regimen. Patients who meet the inclusion/exclusion criteria will sign an informed consent form before undergoing cord blood transplantation. The efficacy (12-month EFS) and safety of the regimen will be assessed 12 months after transplantation.

Inclusion: Subjects suitable for enrollment in this study must meet all of the following criteria:; Age ≥18 years and <50 years, regardless of gender; Diagnosis of AA according to the guidelines of the British Society for Haematology. The bone marrow shows hypocellularity, without infiltration of abnormal cells or marrow fibrosis. The peripheral blood must meet at least two of the following three criteria: absolute neutrophil count (ANC) <1.5×10⁹/L; platelet count <50×10⁹/L; hemoglobin <100 g/L. Based on the severity of the disease, AA is classified into severe aplastic anemia (SAA) and non-severe aplastic anemia (NSAA); The diagnostic criteria for severe aplastic anemia (SAA) are as follows:; Peripheral blood criteria; At least two of the following three criteria must be met:; Absolute neutrophil count (ANC) <0.5×10⁹/L; Reticulocyte count <20×10⁹/L; Platelet count <20×10⁹/L; Bone marrow criteria The degree of bone marrow cellularity is <25% of normal; if ≥25% but <50% of normal, then the proportion of residual hematopoietic cells should be <30%; Bone marrow aspiration results show hypocellular or severely hypocellular marrow, with a marked decrease in hematopoietic cells and an increase in non-hematopoietic cells such as lymphocytes and reticular cells; Other：Other diseases causing pancytopenia, such as myelodysplastic syndrome (MDS), paroxysmal nocturnal hemoglobinuria (PNH), and congenital marrow failure syndromes, should be excluded; If ANC <0.2×10⁹/L, the diagnosis is very severe aplastic anemia (VSAA); Those who do not meet the criteria for SAA are classified as non-severe aplastic anemia (NSAA); Meet the criteria for refractory AA: ①SAA: no response to first-line ATG + CSA treatment for more than 6 months; ②NSAA: ①persistent transfusion dependence of two or more blood cell lines, ②meet any of the following criteria: no response to immunosuppressive therapy with cyclosporine for more than 12 months, or no response to androgen and/or TPO receptor agonist therapy for more than 6 months, ④or progression to SAA; Meet the criteria for relapsed AA: initially effective to first-line immunosuppressive therapy, but pancytopenia recurs after reduction or discontinuation of immunosuppressive therapy, meeting the criteria for SAA; Karnofsky score ≥60, ECOG score ≤2, HCT-CI index ≤2; No HLA-identical sibling donor or no HLA-identical unrelated donor available; Understanding of the study procedures and voluntary written informed consent.

Exclusion: Subjects with any of the following conditions are not eligible for enrollment in this study:; Pancytopenia and hypoplastic marrow diseases caused by other reasons (including PNH, etc.); Use of intermediate or high doses of cyclophosphamide (≥20mg/kg/d) for immunosuppressive therapy within 3 months before enrollment; History of hematopoietic stem cell transplantation; Known or suspected contraindications or allergies to fludarabine, melphalan, or other drugs; Patients with uncontrolled bleeding and/or infection after standard treatment before screening; Active viral hepatitis (hepatitis B, hepatitis C, etc.), HIV infection, or syphilis at baseline or screening; Creatinine clearance rate <60 ml/min before treatment, or serum creatinine >140 μmol/L; Pregnant or breastfeeding women; Participation in another clinical trial within 3 months before enrollment; Any other condition that the investigator deems may prevent the subject from completing the study or pose significant risks to the subject.

ClinicalTrials.gov NCT07078721