Human Leukocyte Antigen (HLA) Mismatched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation

Phase 1

Recruiting

• Conditions: Hematologic Disease
• Interventions: Drug: Busulfan (Busulfex); Drug: Cyclophosphamide (CTX); Drug: Fludarabine (Fludara); Drug: Semustine (MeccNU)

• Registration Number: NCT06809712
• Lead Sponsor: He Huang

Brief Summary

This study is a single center, prospective, single arm exploratory clinical trial that includes patients with hematological malignancies who are indicated for allogeneic hematopoietic stem cell transplantation (allo HSCT) but lack suitable donors. This project plans to use highly mismatched unrelated HLA mismatched donors. Ultimately, an unrelated human leukocyte antigen (HLA) mismatched allo HSCT transplantation plan will be established to improve the disease prognosis of this group of patients and truly enter the era of "everyone has a donor" for allo HSCT.

Detailed Description

This study is a single center, prospective, single arm exploratory clinical trial that includes patients with hematological malignancies who are indicated for allogeneic hematopoietic stem cell transplantation (allo HSCT) but lack suitable donors. This project plans to use highly mismatched unrelated HLA mismatched donors. Ultimately, an unrelated human leukocyte antigen (HLA) mismatched allo HSCT transplantation plan will be established to improve the disease prognosis of this group of patients and truly enter the era of "everyone has a donor" for allo HSCT.

Study Timeline

• Study Start: 2022-08-04
• Status Verified: 2024-10
• Study First Submitted: 2024-10-04
• Study First Submitted QC: 2025-01-30
• Last Update Submitted: 2025-01-30
• Study First Posted: 2025-02-05
• Last Update Posted: 2025-02-05
• Primary Completion: 2026-10-31
• Study Completion: 2027-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Adult patients (18-60 years old) with hematological malignancies and indications for hematopoietic stem cell transplantation;
• Non blood donors without human leukocyte antigen (HLA) high-resolution typing ≥ 9/10, or those who have difficulty finding non blood donors due to urgent medical conditions;
• No suitable HLA matching haploidentical donor available;
• There are suitable unrelated HLA mismatched (HLA high-resolution typing<9/10) donors;
• The subjects or their legal representatives shall sign an informed consent form before the start of the clinical study.

Exclusion Criteria

• Patients with severe liver and kidney function (alanine aminotransferase>2.5 times the upper limit of normal, blood creatinine>1.5 times the upper limit of normal) and cardiopulmonary dysfunction (New York Heart Association (NYHA) III/IV heart function, ejection fraction<50%, severe obstructive or restrictive ventilation dysfunction);
• Merge active infections;
• Eastern Cooperative Oncology Group Performance Status (ECOG) score ≥ 2 points;
• Secondary tumors with merged activity;
• Severe central nervous system or mental illness leading to the inability to autonomously choose to enter or exit clinical trials;
• Combine other allo hematopoietic stem cell transplantation (HSCT) contraindications.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HLA mismatch	Busulfan (Busulfex)	Myeloablative conditioning regimen was used when patient is below 50 and with a HCT-CI score \<2; Reduced intensity conditioning regimen was used when patient is over 50 or with HCT-CI score ≥2.
HLA mismatch	Cyclophosphamide (CTX)	Myeloablative conditioning regimen was used when patient is below 50 and with a HCT-CI score \<2; Reduced intensity conditioning regimen was used when patient is over 50 or with HCT-CI score ≥2.
HLA mismatch	Fludarabine (Fludara)	Myeloablative conditioning regimen was used when patient is below 50 and with a HCT-CI score \<2; Reduced intensity conditioning regimen was used when patient is over 50 or with HCT-CI score ≥2.
HLA mismatch	Semustine (MeccNU)	Myeloablative conditioning regimen was used when patient is below 50 and with a HCT-CI score \<2; Reduced intensity conditioning regimen was used when patient is over 50 or with HCT-CI score ≥2.

Primary Outcome Measures

Name	Time	Method
Overall survival	1-year	Overall survival (OS) after allogeneic hematopoietic cell transplantation is defined as the proportion of patients who are alive at a specified time point following the transplantation, regardless of disease status or cause of death.

Secondary Outcome Measures

Name	Time	Method
Neutrophil engraftment rate	28-days	The 28-day neutrophil engraftment rate is assessed, with neutrophil engraftment defined as achievement of an absolute neutrophil count (ANC) of ≥ 0.5 × 10⁹/L for three consecutive days.
Platelet engraftment rate	28-days	The 28-day platelet engraftment rate is assessed, with platelet engraftment defined as achievement of a platelet count of ≥ 20 × 10⁹/L without transfusion support for at least seven consecutive days.
GVHD	180 days and 2 year	Cumulative incidence of aGvHD and cGvHD in different target organs and overall population.
Relapse	1-year	Cumulative incidence of disease relapse after transplantation.
Progression-free survival	1-year	Progression-free survival (PFS) after allogeneic hematopoietic cell transplantation is defined as the length of time a patient survives without evidence of disease progression or relapse following the transplantation.
Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS)	1-year	Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation is defined as the time a patient survives without experiencing grade III-IV acute GVHD, severe chronic GVHD, relapse, or death.

Trial Locations

Locations (1)

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, China