Dexamethasone, Intravenous Injection of Human Immunoglobulin, and Increased Infusion of Mononuclear Cells to Reduce Donor Specific Antibodies in Haploidentical Hematopoietic Stem Cell Transplantation

Official title

Dexamethasone, Intravenous Injection of Human Immunoglobulin, and Increased Infusion of Mononuclear Cells to Reduce Donor Specific Antibodies in Haploid Hematopoietic Stem Cell Transplantation: a Prospective, Multicenter Study

Overview

This study tests whether a combination of three treatments - dexamethasone (a steroid), intravenous immunoglobulin (IVIG, a protein that helps the immune system), and an extra dose of donor mononuclear cells - can safely lower harmful antibodies called donor-specific antibodies (DSA) in patients who need a stem cell transplant from a half-matched (haploidentical) family donor. In these transplants, DSA are antibodies made by the patient's own body that attack the donor's stem cells. If DSA levels are high, the transplant is more likely to fail - the donor cells may not "take" (engraft). Currently, there is no single, simple, and reliable way to reduce DSA, and many existing methods have drawbacks. Based on the investigators' earlier experience in 11 patients, this three-part approach seemed to work well. All patients successfully engrafted, and DSA levels dropped quickly. Now the study team want to confirm these results in a larger, prospective, multicenter study. The investigators plan to enroll 60 patients aged 18-65 with blood cancers or other blood disorders who need a haploidentical transplant, have DSA levels above 500 MFI (a measure of antibody strength), and have no other suitable donor available. Participants will receive: * Dexamethasone (25 mg/m²) for 4 days before transplant, * IVIG (1 g/kg) one day before transplant, * Extra mononuclear cells on transplant day - the extra amount depends on how high their DSA level is (low, medium, or high). The main goal is to see how many patients have primary graft failure (when the donor cells never engraft). The study team will also measure how long it takes for blood counts to recover, rates of graft-versus-host disease, survival, and side effects. All participants will be followed for 1 year. This study will help the investigators find out whether this combination is a safe, simple, and effective way to improve transplant success for patients with DSA who have no other donor options.

Interventions

• Biological Intravenous Immunoglobulin
  1 g/kg intravenously on day -1 prior to transplant.
• Drug Dexamethasone
  25 mg/m² intravenously for 4 days prior to transplant (days -4 to -1).
• Biological Mononuclear Cells
  Additional donor MNCs infused on day 0. Dose stratified by baseline DSA MFI level: ≤5000: +2±2×10⁸/kg; 5000-10000: +4±2×10⁸/kg; \>10000: +6±2×10⁸/kg.

Primary outcome measures

• Primary Graft Failure (PGF) [Time frame: Day +28 post-transplant]

Secondary outcome measures (5)

• Neutrophil and Platelet Engraftment Time [Time frame: Up to 28 days post-transplant]
• Dynamic Changes in Donor-Specific Antibody (DSA) MFI Levels [Time frame: Pre-transplant (day -14 to -1) through day +22 post-transplant]
• Incidence of Acute and Chronic Graft-Versus-Host Disease [Time frame: Up to 1 year post-transplant]
• Overall Survival and Disease-Free Survival [Time frame: Up to 1 year post-transplant]
• Incidence of Adverse Events [Time frame: Up to 1 year post-transplant]

Eligibility criteria

Inclusion criteria

• Diagnosis of benign or malignant hematological diseases (including leukemia, lymphoma, thalassemia, aplastic anemia, myelodysplastic syndromes, etc.) confirmed by NCCN guidelines, and determined by the investigator to require allogeneic hematopoietic stem cell transplantation.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.
• Donor-specific antibody (DSA) mean fluorescence intensity (MFI) > 500.
• Age between 18 and 65 years (age limits are also captured separately in the eligibility module).
• Body weight between 40 kg and 100 kg.
• No other suitable donor available (i.e., no DSA-negative related donor or unrelated donor).

Exclusion criteria

• Patients unsuitable for transplantation or without willingness to undergo transplantation, or diagnosed with non-hematological diseases.
• Estimated life expectancy < 1 month.
• Known allergy to any drug or intervention used in the study regimen.
• Pregnancy, lactation, active severe infection, or severe major organ dysfunction.
• Severe psychiatric or neurological disorders that may affect the ability to provide informed consent and/or to report adverse events or comply with observation.
• Refusal or inability to sign the informed consent form.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07698080 · KM-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗