Clinical trial NCT06362967: The Efficacy and Safety of Desensitation Regimen for Patients With High Titers of Anti-HLA Antibodies Prior to Allo-HSCT
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: High Titers of Anti-HLA Antibody (MFI ≥5000)
Keywords: immunoadsorption or plasma exchange；rituximab；high-dose IVIG
Lead sponsor: Anhui Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2024-04-12
Enrollment: 30
Sex: ALL
Minimum age (years): 14
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of reduction of anti-HLA antibody MFI values to less than 5000 in subjects at the end of treatment
timeFrame: at the end of desensitation treatment
Secondary outcomes:
measure: Incidence of primary graft failure
timeFrame: 42 days
measure: Incidence of TRM after allo-HSCT
timeFrame: 100 days
measure: Incidence of ineffective platelet transfusion after allo-HSCT
timeFrame: 100 days
measure: Cumulative incidence of neutrophil engraftment after allo-HSCT
timeFrame: 42 dyas
measure: Cumulative incidence of II-IV° acute GVHD
timeFrame: 100 days
measure: Cumulative incidence of relapse at 1 year post-transplant
timeFrame: 360 days
measure: Probability of overall survival post transplantation
timeFrame: 360 days
measure: Incidence of allergies and allergic reactions
timeFrame: at the end of desensitation treatment
measure: Incidence of haemorrhagic events
timeFrame: at the end of desensitation treatment
measure: Incidence of viral, bacterial and fungal infections
timeFrame: at the end of desensitation treatment
measure: Incidence of hypocalcaemia
timeFrame: at the end of desensitation treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
state: Anhui
Study officials:
affiliation: The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
name: Xiaoyu Zhu, ph.D.
role: PRINCIPAL_INVESTIGATOR
References: