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

Phase 1

Recruiting

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

• Registration Number: NCT06809699
• 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 human leukocyte antigen (HLA) mismatched donors. Ultimately, a HLA mismatched allo HSCT transplantation plan will be established to improve the disease prognosis of these patients and truly enter the era of "everyone has a donor".

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 human leukocyte antigen (HLA) mismatched donors. Ultimately, a HLA mismatched allo HSCT transplantation plan will be established to improve the disease prognosis of these patients and truly enter the era of "everyone has a donor".

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 with no available related human leukocyte antigen (HLA) identical sibling donors;
• No available donor with HLA high-resolution typing ≥ 9/10 or those who have difficulty finding donors due to urgent medical conditions;
• No suitable HLA matching haploidentical donor available;
• There is a suitable donor with mismatched HLA typing;
• 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 (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 HSCT contraindications.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HLA-mismatch related	Busulfan (Busulfex)	The myeloablative conditioning is used when the patient is below 50 and with an HCT-CI\<2. The reduced intensity conditioning is used when the patient is over 50 or with an HCT-CI≥2.
HLA-mismatch related	Cyclophosphamide (CTX)	The myeloablative conditioning is used when the patient is below 50 and with an HCT-CI\<2. The reduced intensity conditioning is used when the patient is over 50 or with an HCT-CI≥2.
HLA-mismatch related	Fludarabine (Fludara)	The myeloablative conditioning is used when the patient is below 50 and with an HCT-CI\<2. The reduced intensity conditioning is used when the patient is over 50 or with an HCT-CI≥2.
HLA-mismatch related	Semustine (MeCCNU)	The myeloablative conditioning is used when the patient is below 50 and with an HCT-CI\<2. The reduced intensity conditioning is used when the patient is over 50 or with an HCT-CI≥2.

Primary Outcome Measures

Name	Time	Method
Overall survival	1-year	Overall survival after allogeneic cell transplantation refers to the length of time a patient remains alive from the date of transplantation, regardless of disease status or complications.

Secondary Outcome Measures

Name	Time	Method
Neutrophil engraftment rate	28 days	The neutrophil engraftment rate is assessed, and neutrophil engraftment is defined as achievement of an absolute neutrophil count (ANC) of ≥ 0.5 × 10⁹/L for three consecutive days
Platelet engraftment rate	28 days	Platelet engraftment rate is assessed, and platelet engraftment is defined as achievement of a platelet count of ≥ 20 × 10⁹/L (or ≥ 50 × 10⁹/L in some definitions) without transfusion support for at least seven consecutive days.
Relapse	1-year	Cumulative incidence of relapse
Cumulative incidence of relapse	1-year	Progression-free survival after allogeneic cell transplantation refers to the length of time during which a patient remains alive without any signs of disease relapse or progression.
Progression free survival	1-year	Progression-free survival after allogeneic cell transplantation refers to the length of time during which a patient remains alive without any signs of disease relapse or progression.
GRFS	1-year	GRFS (Graft-versus-host disease-free, relapse-free survival) after allogeneic cell transplantation is the length of time a patient remains alive without experiencing significant graft-versus-host disease, disease relapse, or death.

Trial Locations

Locations (1)

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