Severe Aplastic Anemia, Severe Aplastic Anemia, Refractory, Severe Aplastic Anemia (SAA)
Conditions
Keywords
Severe Aplastic Anemia, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells
Brief summary
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
Detailed 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).
Interventions
DRUG3D hypoxia-preconditioned UC-MSC group
5 × 10⁵/kg 3D hypoxia-preconditioned UC-MSCs at 4 h before HSC infusion
DRUG2D UC-MSC group
5 × 10⁵/kg 2D UC-MSCs at 4 h before HSC infusion
Sponsors
Chinese PLA General Hospital
Fourth Medical Center of PLA General Hospital
Beijing 302 Hospital
The First Medical Center of Chinese PLA General Hospital
Pollon Life Co., Ltd.
Yan'an University Affiliated Hospital
The University of Hong Kong-Shenzhen Hospital
Beijing Friendship Hospital
Beijing GeniusCure Biotechnology Co., Ltd.
Shenzhen University General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 60 Years
Healthy volunteers
No
Inclusion 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).
Exclusion criteria
：(1)Age 6 years or \> 60 years; (2)Failure to meet the IAASG-defined diagnosis of SAA/vSAA, or confirmed (3)Fanconi anemia, congenital aplastic anemia (e.g., dyskeratosis congenita, Diamond-Blackfan anemia); (4)Presence of severe pulmonary, cardiac, hepatic, or renal insufficiency; Uncontrolled active infection; (5)Eastern Cooperative Oncology Group (ECOG) performance status score ≥ 3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events | The incidence and severity of adverse events (AEs) within the first 150 days after haplo-HSCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| acute GVHD | 100days after HSCT | — |
| chronic GVHD | 1 years after HSCT | — |
| Surivial | 1 year after HSCT | — |
| Rates of relapse | UP to 2 years after HSCT | — |
| The implantation | Up to 4 weeks after HSCT | The implantation rate and implantation time. |
Countries
China
Outcome results
None listed