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

Severe Aplastic Anemia Clinical Trial

Official title:

Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired Severe Aplastic Aplasia Receiving Single Cord Blood Transplant: A Multi-center, Single-arm Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06039436
• Other study ID #: CBSAA001
• Status: Recruiting
• Start date: October 2023
• Est. completion date: May 31, 2025

Study information

• Verified date: October 2023
• Source: Anhui Provincial Hospital
• Contact: Xiaoyu Zhu, ph.D
• Phone: 15255456091
• Email: xiaoyuz[@]ustc.edu.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: May 31, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Drug:
• Anti-Thymocyte Globulin (Rabbit)
Indications for trial stopping: subjects occur pregnancy events, severe organ function impairments, or emergency events related or unrelated to treatment; or subjects are unwilling to continue participating in the clinical trial.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)	Hefei	Anhui

Sponsors (1)

Lead Sponsor	Collaborator
Anhui Provincial Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The one-year probability of GRFS	GRFS is defined as survival without grade III-IV acute GVHD immunosuppression requiring chronic GVHD or relapse.	one year
Secondary	The cumulative incidence of platelet engraftment at 28 days after transplantation	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.	28 days
Secondary	The cumulative incidence of neutrophil engraftment at 28 days after transplantation	Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.	28 days
Secondary	Time of platelet engraftment	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.	28 days
Secondary	Time of neutrophil engraftment	Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.	28 days
Secondary	The cumulative incidence of acute GVHD at 100 days after transplantation	Acute GVHD is defined that occurs within 100 days after transplantation	100 days
Secondary	The cumulative incidence of chronic GVHD at 100 days after transplantation	Chronic GVHD is defined that occurs 100 days after transplantation	one year
Secondary	Immune reconstitution after transplantation	The level of immunoglobulin, T cells, B cells and NK cells reconstitution after transplantation	one year
Secondary	The 180-day probability of TRM	TRM(transplant-related mortality) is defined that death due to any transplant-related cause within 180 days after transplantation	180 days
Secondary	The incidence of infection	Infection is defined as various post-transplant associated infections	one year
Secondary	The one-year probability of OS	OS (overall survival) is defined as the time which begins at diagnosis and up to the time of death	one year
Secondary	The one-year probability of DFS	DFS (disease free survival) is defined as the time from treatment until the recurrence of disease (or death) after transplantation	one year