Phase I Clinical Study of Haploid Hematopoietie Stem CellTransplantation Combined With Hypoxic 3D-Cultured Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Aplastic Anemia

Chinese PLA General Hospital (301 Hospital)

Status and phase

Invitation-only

Phase 2

Phase 1

Conditions

Severe Aplastic Anemia, Refractory

Severe Aplastic Anemia (SAA)

Severe Aplastic Anemia

Treatments

Drug: 2D UC-MSC group

Drug: 3D hypoxia-preconditioned UC-MSC group

Study type

Interventional

Funder types

Other

Identifiers

NCT07299123

S2021-384-01

Details and patient eligibility

About

Efficacy and Safety of Sequential Infusion of Hypoxic 3D-Cultured Umbilical Cord Mesenchymal Stem Cells in Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multicenter, Randomized, Phase 1 Trial

Full description

The enrolled patients with an HLA-haploidentical relative for HSCT received the fludarabine (Flu) + cyclophosphamide (Cy) + antithymocyte globulin (ATG) conditioning regimen. For the patients with acute SAA (SAA-I), intravenous administration of 30 mg/(m2 day) of Flu and 500-800 mg/(m2 day) of Cy was performed from days -5 to -2, and 5μg/(kg day) of ATG was administered from days -4 to -1. For the patients with chronic SAA (SAA-II), the same treatment of ATG and Cy was applied as above with the supplement of 0.6 mg/(kg 6 h) of busulfan (BU) from days -8 to -5 prior to transplantation. Donor selection and hematopoietic stem cell mobilization and collection were conducted based on the consensus of The Chinese Society of Hematology regarding indications, conditioning regimens, and donor selection for allogeneic hematopoietic stem cell transplantation. On day 0, HSCs were infused intravenously. Both groups received 5 × 10⁵/kg UC-MSCs at 4 h before HSC infusion. The control group was transfused with conventional 2D-cultured UC-MSCs, whereas the experimental group received 3D hypoxia-preconditioned UC-MSCs. Standard GVHD prophylaxis consisted of mycophenolate mofetil, cyclosporine A, and methotrexate (MTX).

Enrollment

40 estimated patients

Sex

All

Ages

6 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

The inclusion criteria were (1) age 6 to 60 years; (2) diagnosis of SAA or very SAA according to the International Aplastic Anemia Study Group[21]; (3) without any severe pulmonary, cardiac, liver, or renal diseases or any active infection; and (4) adequate performance status (Eastern Cooperative Oncology Group score 0-2). Fanconi anemia was excluded after evaluation of diepoxybutane-stimulated peripheral blood (PB) chromosome breakages. Patients with congenital aplastic anemia like dyskeratosis or Diamond-Blackfan anemia were also excluded.