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

NCT06809699 | Recruiting Phase 1

• 1 other identifier: MMR-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 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".

Conditions

Hematologic Diseases

Keywords

Hematopoietic cell transplantation; HLA mismatch related; Hematologic diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Neutrophil engraftment rate

  28 days

• Platelet engraftment rate

  28 days

• Relapse

  1-year

• Cumulative incidence of relapse

  1-year

• Progression free survival

  1-year

Study Arms (1)

HLA-mismatch related

EXPERIMENTAL

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

Interventions

Busulfan (Busulfex) DRUG

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)

HLA-mismatch related

Cyclophosphamide (CTX) DRUG

Cyclophosphamide is only used in myeloablative conditioning (Cy，1.8g/m2, -5d, -4d)

HLA-mismatch related

Fludarabine (Fludara) DRUG

For myeloablative conditioning: Fludarabine (Flu，30 mg/m2/d IV -6d \~ -2d) For reduced intensity conditioning: Fludarabine（Flu，30mg/m2 /d IV -10d\~-5d）

HLA-mismatch related

Semustine (MeCCNU) DRUG

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

HLA-mismatch related

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 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.

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 (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.

Sponsors & Collaborators

• He Huang: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, China, 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

Yanmin Zhao, MD., PhD

CONTACT

+86 87236706; yanminzhao@zju.edu.cn

Yishan Ye, MD., PhD

CONTACT

yeyishan@zju.edu.cn

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)