The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA

November 15, 2023 updated by: Xiao-Jun Huang, Peking University People's Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100044
        • Recruiting
        • Deparment of Hematology, Peking University People's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Busulfan included group
The conditioning regimens were Bu/Flu/Cy/ATG or Bu/Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.
Drug: Busulfan
Conditioning regimens were Bu/Flu/Cy/ATG or Bu/Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.
Other: Control group
The conditioning regimens were Flu/Cy/ATG or Cy/ATG, depending on the patient's risk factors of regimen related cardiotoxicity.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure free survival
Time Frame: 1 year post HSCT
Failure free survival was defined as survival with a response to therapy.
1 year post HSCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of mixed chimerism
Time Frame: 1 year post HSCT
The mixed chimerism was defined as the presence of 5%-95% donor haematopoietic cells.
1 year post HSCT
Regimen related toxicity
Time Frame: 100 days post HSCT
The regimen related toxicity (RTT) was measured according to the Seattle Toxicity Criteria (Bearman et al, 1988).
100 days post HSCT
Myeloid and platelet engraftment
Time Frame: 100 days post HSCT
Myeloid and platelet engraftment were defined as international criteria.
100 days post HSCT
The incidence of graft versus host disease
Time Frame: 100 days post HSCT for aGvHD and 1 year post HSCT for cGvHD
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
The incidence of CMV and EBV reactivation
Time Frame: 100 days post HSCT
The incidence of CMV and EBV reactivation was defined as CMV and EBV viremia.
100 days post HSCT
The incidence of Transplantation related mortality
Time Frame: 1 year post HSCT
Transplantation related mortality was defined as death without disease progression.
1 year post HSCT
The probability of Overall survival
Time Frame: 1 year post HSCT
Overall survival was defined as the time from transplantation to death from any cause or to the last follow-up
1 year post HSCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Investigators

  • Principal Investigator: Xiao-Jun Huang, Peking University People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2023

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 1, 2023

First Submitted That Met QC Criteria

October 1, 2023

First Posted (Actual)

October 5, 2023

Study Record Updates

Last Update Posted (Estimated)

November 17, 2023

Last Update Submitted That Met QC Criteria

November 15, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023PHB232-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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