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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Severe Aplastic Anemia
• Intervention / Treatment: Drug: Anti-Thymocyte Globulin (Rabbit)

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.

• Study Type: Observational
• Enrollment (Estimated): 72

Contacts and Locations

• Study Contact: Name: Xiaoyu Zhu, ph.D; Phone Number: 15255456091; Email: xiaoyuz@ustc.edu.cn
• Study Contact Backup: Name: Baolin Tang, M.D; Phone Number: 13856901277; Email: zwcrystalbl@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230036
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
      • Contact: Xiaoyu Zhu, ph.D; Phone Number: 15255456091; Email: xiaoyuz@ustc.cn
      • Contact: Baolin Tang, M.D; Phone Number: 13856901277; Email: zwcrystalbl@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

patients with indications for hematopoietic stem cell transplantation and initially diagnosed with severe aplastic anemia or have not responded to immunosuppressive therapy

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ATG group; Patients in the ATG group will be treated with conditioning regimen containing ATG 2mg/kg on day -7 prior to transplant.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Time of neutrophil engraftment	Neutrophil engraftment is defined as neutrophil count achieves 0.5 ×10^9/L for three consecutive days.	28 days
The cumulative incidence of acute GVHD at 100 days after transplantation	Acute GVHD is defined that occurs within 100 days after transplantation	100 days
The cumulative incidence of chronic GVHD at 100 days after transplantation	Chronic GVHD is defined that occurs 100 days after transplantation	one year
Immune reconstitution after transplantation	The level of immunoglobulin, T cells, B cells and NK cells reconstitution after transplantation	one year
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
The incidence of infection	Infection is defined as various post-transplant associated infections	one year
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
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

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Xiaoyu Zhu, ph.D, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provicial Hospital)

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: September 9, 2023
• First Submitted That Met QC Criteria: September 9, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 22, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Severe Aplastic Anemia; Anti-Thymocyte Globulin (Rabbit); Umbilical Cord Blood Transplantation
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Anemia; Bone Marrow Failure Disorders; Anemia, Aplastic; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Thymoglobulin; Antilymphocyte Serum
• Other Study ID Numbers: CBSAA001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No