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

NCT06809712 | Recruiting Phase 1

• 1 other identifier: MMU-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematologic Disease

Keywords

Hematopoietic cell transplantation; HLA mismatch; Hematologic diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Neutrophil engraftment rate

  28-days

• Platelet engraftment rate

  28-days

• GVHD

  180 days and 2 year

• Relapse

  1-year

• Progression-free survival

  1-year

Study Arms (1)

HLA mismatch

EXPERIMENTAL

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); Drug: Cyclophosphamide (CTX); Drug: Fludarabine (Fludara); Drug: Semustine (MeccNU)

Interventions

Busulfan (Busulfex) DRUG

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);

HLA mismatch

Cyclophosphamide (CTX) DRUG

Myeloablative conditioning: Cyclophosphamide (Cy，1.8g/m2, -5d, -4d) Cyclophosphamide is not used for reduced intensity conditioning

HLA mismatch

Fludarabine (Fludara) DRUG

Myeloablative conditioning: Fludarabine (Flu，30 mg/m2/d IV -6d \~ -2d); Reduced intensity conditioning: Fludarabine (Flu，30mg/m2 /d IV -10d\~-5d);

HLA mismatch

Semustine (MeccNU) DRUG

For both myeloablative and reduced intensity conditioning: Semustine (MeCCNU: 250 mg/m2 orally-3d)

HLA mismatch

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• He Huang: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, 310003, China

RECRUITING

MeSH Terms

Conditions

Hematologic Diseases

Interventions

Busulfan; Cyclophosphamide; fludarabine; fludarabine phosphate; Semustine

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Lomustine; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Central Study Contacts

Yishan Ye, MD., PhD

CONTACT

+8618268068056; yeyishan@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Director of the Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine

Study Record Dates

• First Submitted: October 4, 2024
• First Posted: February 5, 2025
• Study Start: August 4, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027
• Last Updated: February 5, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)