The Efficacy and Safety of Desensitation Regimen for Patients With High Titers of Anti-HLA Antibodies Prior to Allo-HSCT

The Efficacy and Safety of Immunosorbent or Plasma Exchange Combined With Rituximab and High-dose IVIG for Patients With High Titers of Anti-HLA Antibodies Prior to Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Centre, Single-Arm, Phase II Clinical Study

Evaluation of the efficacy and safety of immunoadsorption or plasma exchange combined with rituximab and high-dose IVIG to reduce high titres of anti-HLA antibodies in patients prior to allogeneic haematopoietic stem cell transplantation

Study Overview

• Status: Not yet recruiting
• Conditions: High Titers of Anti-HLA Antibody (MFI ≥5000)
• Intervention / Treatment: Combination product: Immunoadsorption or plasma exchange combined with rituximab, high-dose IVIG

Detailed Description

Approximately 10-21% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients have non-specific or donor-specific anti-HLA antibodies (DSAs) prior to transplantation. Patients with combined DSAs and mean fluorescence intensity (MFI) ≥ 5000 can lead to a significantly higher incidence of primary graft failure and graft dysfunction after transplantation, and increased transplant-related mortality (TRM). Meanwhile, a retrospective study at our centre found that patients with high titre non-specific antibodies (MFI ≥ 5000) present before cord blood transplantation had significantly higher TRM in the early post-transplantation period. Therefore, our centre intends to conduct a single-arm prospective cohort study to explore whether the desensitisation regimen of immunosorbent or plasma exchange combined with rituximab and high-dose IVIG before transplantation in allogeneic hematopoietic stem cell transplantation patients with high titres of anti-HLA antibodies can lower the antibody titres in the patient's body, reduce the incidence of transplant-related complications, and improve the prognosis of transplantation.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoyu Zhu, ph.D.; Phone Number: 15255456091; Email: xiaoyuz@ustc.edu.cn
• Study Contact Backup: Name: Yue Wu, M.D.; Phone Number: 13805601119; Email: 287109658@qq.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230036
      • The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects to undergo allo-HSCT
2. Age 14-60, No gender, No ethnicity
3. ECOG score ≤ 2
4. Population reactive antibody screening within 1 month prior to transplantation HLA-class I or class II antibody MFI ≥ 5000
5. No severe organ failure and no active infections
6. Subjects and their families voluntarily undergo anti-HLA antibody testing and antibody desensitisation treatment and sign an informed consent form

Exclusion Criteria:

1. Those with severe organ dysfunction or disease, such as severe disease and dysfunction of the heart, liver, kidneys and pancreas
2. Pregnancy
3. Subjects and/or authorised family members who refuse to accept antibody desensitisation treatment
4. Persons with any life-threatening disease, physical condition, or organ system dysfunction that, in the opinion of the investigator, may compromise the safety of the subject and place the results of the study at unnecessary risk
5. Persons with drug dependence,uncontrolled psychiatric disorders and persons with cognitive dysfunction
6. Participants in other clinical studies within 3 months
7. Those whom the investigator considers unsuitable for enrolment (e.g., subjects will not be able to adhere to examinations and treatments due to financial or other issues)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: antibody desensitisation group; Immunoadsorption or plasma exchange combined with rituximab, high-dose IVIG

Combination product: Immunoadsorption or plasma exchange combined with rituximab, high-dose IVIG; For allogeneic haematopoietic stem cell transplantation patients with high titers of anti-HLA antibodies present in the body, a desensitisation regimen of immunosorbent or plasma exchange combined with rituximab and high-dose IVIG is used prior to transplantation.; Other Names: Intravenous Immunoglobin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of reduction of anti-HLA antibody MFI values to less than 5000 in subjects at the end of treatment	Incidence of reduction of anti-HLA antibody MFI values to less than 5000 in subjects at the end of treatment	at the end of desensitation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of primary graft failure	Incidence of primary graft failure	42 days
Incidence of TRM after allo-HSCT	Incidence of TRM after allo-HSCT	100 days
Incidence of ineffective platelet transfusion after allo-HSCT	Incidence of ineffective platelet transfusion after allo-HSCT	100 days
Cumulative incidence of neutrophil engraftment after allo-HSCT	Cumulative incidence of neutrophil engraftment after allo-HSCT cumulative incidence of neutrophil engraftment after allo-HSCT	42 dyas
Cumulative incidence of II-IV° acute GVHD	Cumulative incidence of II-IV° acute GVHD	100 days
Cumulative incidence of relapse at 1 year post-transplant	Cumulative incidence of relapse at 1 year post-transplant	360 days
Probability of overall survival post transplantation	Probability of overall survival post transplantation	360 days
Incidence of allergies and allergic reactions	Incidence of allergies and allergic reactions	at the end of desensitation treatment
Incidence of haemorrhagic events	Incidence of haemorrhagic events	at the end of desensitation treatment
Incidence of viral, bacterial and fungal infections	Incidence of viral, bacterial and fungal infections	at the end of desensitation treatment
Incidence of hypocalcaemia	Incidence of hypocalcaemia	at the end of desensitation treatment

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Xiaoyu Zhu, ph.D., The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunoadsorption or plasma exchange；rituximab；high-dose IVIG
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: Anti-HLA antibody

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
• product manufactured in and exported from the U.S.: No