The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA

Severe Aplastic Anemia Clinical Trial

Official title:

To Evaluate Different Conditioning Regimens for HLA Matched Donor Transplantation in Severe Aplastic Anemia: a Prospective, Multicenter, Randomized Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06069180
• Other study ID #: 2023PHB232-001
• Status: Recruiting
• Phase: Phase 4
• Start date: November 15, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: Peking University People's Hospital
• Contact: Zheng-Li Xu, M.D.
• Phone: +8613501338951
• Email: xuzhengli0202[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA) -matched donor is an effective option for severe aplastic anemia (SAA), but there is no standardized and recommended conditioning regimen. The occurrence of mixed chimerism after transplantation is associated with secondary graft failure and poor failure-free survival. Previous studies have shown that Fludarabine (Flu)/ Cyclophosphamide (Cy)/ antithymocyte globulin (antithymocyte globulin), ATG) and Cy/ATG conditioning regimens had higher rates of mixed chimerism and poorer failure-free survival. A small cohort study has suggested that adding busulfan to Flu/Cy/ATG or Cy/ATG can reduce the incidence of mixed chimerism and improve failure-free survival. This study was a prospective, multicenter, randomized controlled trial to compare the efficacy and safety of different conditioning regimens in the treatment of severe aplastic anemia (SAA) after hematopoietic stem cell transplantation (HSCT) from HLA-identical sibling or unrelated donor.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 50 Years

Eligibility

Inclusion Criteria:

1. Diagnosed as SAA/vSAA

2. Indication for hematopoietic stem cell transplantation

3. Available HLA matched sibling or unrelated donor

4. No active infection

5. No serious organ damage: liver and kidney function (ALT and AST < 2.5 times normal value, normal renal function, no cardiac insufficiency)

6. Signed informed consent

7. High risk factors of mixed chimerism, at least one of the following

1. Age < 18 years old

2. Ferritin level =2500ng/ml before transplantation

Exclusion Criteria:

1. Age > 50 years old

2. ECOG=3

3. Active infections that were difficult to control

4. Severe liver and kidney dysfunction

5. Mental illness

6. Not signing the informed consent

7. pregnant or lactating women

8. Any condition considered by the investigators to be unsuitable for enrollment

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Drug:
• Busulfan
Conditioning regimens were Bu/Flu/Cy/ATG or Bu/Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.
• Flu/Cy/ATG or Cy/ATG
Conditioning regimens were Flu/Cy/ATG or Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.

Locations

Country	Name	City	State
China	Deparment of Hematology, Peking University People's Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure free survival	Failure free survival was defined as survival with a response to therapy.	1 year post HSCT
Secondary	The incidence of mixed chimerism	The mixed chimerism was defined as the presence of 5%-95% donor haematopoietic cells.	1 year post HSCT
Secondary	Regimen related toxicity	The regimen related toxicity (RTT) was measured according to the Seattle Toxicity Criteria (Bearman et al, 1988).	100 days post HSCT
Secondary	Myeloid and platelet engraftment	Myeloid and platelet engraftment were defined as international criteria.	100 days post HSCT
Secondary	The incidence of graft versus host disease	The severity of acute and chronic GVHD was evaluated according to standard criteria.	100 days post HSCT for aGvHD and 1 year post HSCT for cGvHD
Secondary	The incidence of CMV and EBV reactivation	The incidence of CMV and EBV reactivation was defined as CMV and EBV viremia.	100 days post HSCT
Secondary	The incidence of Transplantation related mortality	Transplantation related mortality was defined as death without disease progression.	1 year post HSCT
Secondary	The probability of Overall survival	Overall survival was defined as the time from transplantation to death from any cause or to the last follow-up	1 year post HSCT