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

A Prospective Single-arm Trial on Human Leukocyte Antigen (HLA) Mismatched Unrelated 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 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 Overview

• Status: Recruiting
• Conditions: Hematologic Disease
• 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 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 Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yishan Ye, MD., PhD; Phone Number: +8618268068056; Email: yeyishan@hotmail.com

Study Locations

• China
  • Hangzhou, China, 310003
    • Recruiting
    • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Contact: He Huang
    • Contact: Yishan Ye; Phone Number: +86 57187236706; Email: yeyishan@zju.edu.cn
    • Contact: Yishan Ye, 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;
• 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 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; 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.

Drug: Busulfan (Busulfex); Myeloablative conditioning: Busulfan (Bu，3.2 mg/kg/d IV -8d ~-6d); Reduced intensity conditioning: Busulfan (Bu，3.2 mg/kg/d IV -7d~-5d); Drug: Cyclophosphamide (CTX); Myeloablative conditioning: Cyclophosphamide (Cy，1.8g/m2, -5d, -4d) Cyclophosphamide is not used for reduced intensity conditioning; Drug: Fludarabine (Fludara); Myeloablative conditioning: Fludarabine (Flu，30 mg/m2/d IV -6d ~ -2d); 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 (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.	1-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil engraftment rate	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.	28-days
Platelet engraftment rate	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.	28-days
GVHD	Cumulative incidence of aGvHD and cGvHD in different target organs and overall population.	180 days and 2 year
Relapse	Cumulative incidence of disease relapse after transplantation.	1-year
Progression-free survival	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.	1-year
Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS)	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.	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
• 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: MMU-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