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

A Prospective Single-arm Trial on Human Leukocyte Antigen (HLA) Mismatched Related Allogeneic Hematopoietic Stem Cell Transplantation

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 Overview

• Status: Recruiting
• Conditions: Hematologic Diseases
• Intervention / Treatment: Drug: Busulfan (Busulfex); Drug: Cyclophosphamide (CTX); Drug: Fludarabine (Fludara); Drug: Semustine (MeCCNU)

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 Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yanmin Zhao, MD., PhD; Phone Number: +86 87236706; Email: yanminzhao@zju.edu.cn
• Study Contact Backup: Name: Yishan Ye, MD., PhD; Email: yeyishan@zju.edu.cn

Study Locations

• China
  • Hangzhou, China, 310003
    • Recruiting
    • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Contact: He Huang
    • Contact: Yanmin Zhao, MD., PhD; Phone Number: +86 57187236706; Email: yanminzhao@zju.edu.cn
    • Contact: Yanmin Zhao, MD., PhD

Participation Criteria

Eligibility Criteria

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

Description

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 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: HLA-mismatch related; 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.

Drug: Busulfan (Busulfex); For myeloablative conditioning: Busulfan (Bu，3.2 mg/kg/d IV -8d ~-6d) For reduced intensity conditioning: (Bu，3.2 mg/kg/d IV -7d~-5d); Drug: Cyclophosphamide (CTX); Cyclophosphamide is only used in myeloablative conditioning (Cy，1.8g/m2, -5d, -4d); Drug: Fludarabine (Fludara); For myeloablative conditioning: Fludarabine (Flu，30 mg/m2/d IV -6d ~ -2d) For reduced intensity conditioning: Fludarabine（Flu，30mg/m2 /d IV -10d~-5d）; Drug: Semustine (MeCCNU); For both myeloablative and reduced intensity conditioning: Semustine (MECCNU，250 mg/m2 orally-3d).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	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.	1-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil engraftment rate	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	28 days
Platelet engraftment rate	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.	28 days
Relapse	Cumulative incidence of relapse	1-year
Cumulative incidence of relapse	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.	1-year
Progression free survival	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.	1-year
GRFS	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.	1-year

Collaborators and Investigators

• Sponsor: He Huang

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: October 4, 2024
• First Submitted That Met QC Criteria: January 30, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Hematopoietic cell transplantation; Hematologic diseases; HLA mismatch related
• Additional Relevant MeSH Terms: Hematologic Diseases; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Busulfan; Semustine
• Other Study ID Numbers: MMR-001

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