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Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired SAA Receiving sUCBT

Recruiting
Conditions
Severe Aplastic Anemia
Interventions
Registration Number
NCT06039436
Lead Sponsor
Anhui Provincial Hospital
Brief Summary

To evaluate the safety and efficacy of Single Umbilical Cord blood transplantation (sUCBT) containing low dose ATG based conditioning regimen in the treatment of acquired Severe Aplastic Anemia (SAA).

Detailed Description

Hematopoietic stem cell transplantation (HSCT) from HLA-compatible sibling donors is the standard preferred therapy for Severe Aplastic Anemia (SAA). At present, HLA-compatible donors in China fail to meet the needs of patients for transplantation. Umbilical Cord blood transplantation (UCBT) is an alternative treatment for patients with emergency conditions who lack compatible sibling donors, have failed immunosuppressant therapies or cannot wait for unrelated fully compatible donors. However, implantation failure is one of the main problems in UCBT for SAA due to the low cord blood stem cells. Nowadays, there is no consensus on the optimal conditioning regimen for UCBT treatment of SAA, and whether ATG should be added to the conditioning regimen is still controversial. Early clinical studies in UCBT have shown that the sufficient ATG in the conditioning regimen will lead to a decrease rate of implantation rate and affect survival of UCBT ultimately. However, a range of recent studies have found that with the addition of low-dose ATG, T cell reconstitution seems to outperform bone marrow or peripheral blood stem cell transplantation. Therefore, how to properly use ATG to both retain its effective GVHD prevention effect and reduce its impact on immune reconstruction has important clinical significance for improving the transplantation efficacy. In this study, a multicenter clinical study will be conducted to observe the safety and efficacy of UCBT with low dose ATG in the treatment of SAA and the long-term quality of life of patients.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
72
Inclusion Criteria
  • Patients diagnosed with severe aplastic anemia who do not respond to initial diagnosis or immunosuppressive therapy;
  • Patients meet diagnostic criteria for severe aplastic anemia (Camitta criteria);
  • Age from 1 to 50 years old, male or female;
  • Patients without HLA-matched sibling or unrelated donors avaliable;
  • Patients who have undergone unrelated cord blood transplantation need to have HLA high-resolution matching、TNC (before cord blood freezing)≥3.0×107/kg、CD34+(before cord blood freezing)≥1.5×107/kg、tubule recovery rate≥80%;
  • patients and their family members or guardians agreed to the study and signed informed consent;
  • No severe organ failure;
  • ECOG score≤2 and HCT-CI≤2;
  • serum ferritin (SF)<1000ug/L;
  • women of reproductive agemust have a negative pregnancy test and agree to use effective contraception during treatment and for one year thereafter.
Exclusion Criteria
  • patients with inherited bone marrow failure syndromes;
  • Positive for HLA-A, B, Cw, DRB1, DQB1, DPB1 site-specific HLA antibodies for donor cord blood with solid-phase fluorescence assay;
  • patients who have previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
  • Uncontrolled bacterial, viral, or fungal infections;
  • HIV infection or active viral hepatitis B or C infection;
  • Pregnant or breastfeeding women;
  • patients with a history of primary malignancy within 3 years prior to transplant treatment;
  • patients receiving ATG treatment within 2 weeks before transplantation;
  • patients with drug dependent or uncontrolled mental illness or cognitive impairment;
  • Participants in other similar clinical studies within 3 months;
  • Patients allergic to ATG;
  • patients considered unsuitable for inclusion by the researchers.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ATG groupAnti-Thymocyte Globulin (Rabbit)Patients in the ATG group will be treated with conditioning regimen containing ATG 2mg/kg on day -7 prior to transplant.
Primary Outcome Measures
NameTimeMethod
The one-year probability of GRFSone year

GRFS is defined as survival without grade III-IV acute GVHD immunosuppression requiring chronic GVHD or relapse.

Secondary Outcome Measures
NameTimeMethod
The cumulative incidence of platelet engraftment at 28 days after transplantation28 days

Platelet engraftment is defined as independent from platelet transfusion for at least 7 days with a platelet count of more than 20 × 10\^9/L.

The cumulative incidence of neutrophil engraftment at 28 days after transplantation28 days

Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10\^9/L for three consecutive days.

Time of neutrophil engraftment28 days

Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10\^9/L for three consecutive days.

The 180-day probability of TRM180 days

TRM(transplant-related mortality) is defined that death due to any transplant-related cause within 180 days after transplantation

The cumulative incidence of chronic GVHD at 100 days after transplantationone year

Chronic GVHD is defined that occurs 100 days after transplantation

Immune reconstitution after transplantationone year

The level of immunoglobulin, T cells, B cells and NK cells reconstitution after transplantation

The incidence of infectionone year

Infection is defined as various post-transplant associated infections

The one-year probability of OSone year

OS (overall survival) is defined as the time which begins at diagnosis and up to the time of death

The one-year probability of DFSone year

DFS (disease free survival) is defined as the time from treatment until the recurrence of disease (or death) after transplantation

Time of platelet engraftment28 days

Platelet engraftment is defined as independent from platelet transfusion for at least 7 days with a platelet count of more than 20 × 10\^9/L.

The cumulative incidence of acute GVHD at 100 days after transplantation100 days

Acute GVHD is defined that occurs within 100 days after transplantation

Trial Locations

Locations (1)

The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)

🇨🇳

Hefei, Anhui, China

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