Clinical Study of Super Transplantation in the Treatment of Severe β-thalassemia

This is a single-arm, open label, phase 1 study in subjects with beta-thalassemia. This study will evaluate the safety and efficacy of preconditioning-free super-transplantation on beta-thalassemia pediatric patients.

Study Overview

• Status: Recruiting
• Conditions: Thalassemia Majors (Beta-Thalassemia Major); Haplo-identical Donors
• Intervention / Treatment: Drug: super-transplantation in 3 severe β -thalassemia pediatric patients.

Detailed Description

Patient screening:

1. Two months before transplantation, pediatric patients are evaluated by our center, and the patients meeting the inclusion criteria will be screened into the group.
2. Investigators and doctors will give detailed information about the benefits and risks of participating in the study, and the informed consents are further signed.

Transplant conduction:

1. Donor mobilization: HLA-fully matched or haplo-identical donors are mobilized subcutaneously for five days with human granulocyte colony-stimulating factor (G-CSF) and the peripheral blood mononuclear cells (PBMCs) that contain a certain numbers of CD34+ stem cells and CD3+ lymphocytes will be extracted by blood cell separators.
2. Transplant regimen: Hydroxycarbamide will be used to reduce the total white blood cells before transplant. However, no traditional transplantation conditioning will be performed, including but not limited to busulfan, fludarabine, Cyclophosphamide, ATG, and irradiation. Splenectomy should be performed if the longitudinal diameter of the spleen exceeds the normal value by 4 cm.
3. Cell infusion: Pediatric patients will be infused with the PBMCs intravenously at day 0.
4. GVHD prophylaxis: The dosage of immunosuppressants is half of the conventional post-transplantation level, but adjustments to the dosage may be necessary based on specific circumstances.
5. Infection management: Antibacterial, antifungal medications, and anti-Pneumocystis medications need to be administered during the period of granulocytopenia. The preemptive treatment for cytomegalovirus will be performed when the virus serological test is positive.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hua Jiang, Doctor; Phone Number: 86-020-38076501; Email: jiang_hua18@sina.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Active, not recruiting
      • Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of severe β -thalassemia
2. Age between 7-10 years old, male and female; Weight < 40kg
3. The patient has or does not have an HLA-compatible or semi-compatible donor, but unconditional transplantation or refusal of blood stem cell transplantation; Patients with thalassemia gene therapy without conditions or refusal;
4. There are fully compatible or incompatible HLA donors, and the physical examination meets the donor conditions;
5. The patient and family members agree to receive hypertransplant therapy and sign a written informed consent prior to the transplant trial.

Exclusion Criteria:

1. Mental patients;
2. Participants in other drug clinical trials within the past 1 month;
3. There are no suitable HLA-incompatible donors.
4. Other researchers decide that it is not suitable to participate in this researcher.

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: Severe β -thalassemia; Children with β-thalassemia major received super transplantation, and chimerism tests were performed at 3 months, 6 months, 9 months, and 1 year after transplantation to evaluate the safety and effectiveness.	Drug: super-transplantation in 3 severe β -thalassemia pediatric patients.; Haplo-identical donors are mobilized with G-CSF and PBMCs that contain CD34+ stem cells and CD3+ lymphocytes will be extracted by blood cell separators. Then the patients will be infused with the PBMC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
chimeric status	Detecting the chimerism in recipients' peripheral blood and bone marrow.Chimerism is generally measured in percentages(%)	1 year after transplantation.

Collaborators and Investigators

• Sponsor: Guangzhou Women and Children's Medical Center
• Investigators: Study Director: Hua Jiang, PHD, Guangzhou Medical University Affiliated Women's and Children's Medical Center

Publications and helpful links

General Publications

• Shafique F, Ali S, Almansouri T, Van Eeden F, Shafi N, Khalid M, Khawaja S, Andleeb S, Hassan MU. Thalassemia, a human blood disorder. Braz J Biol. 2021 Sep 3;83:e246062. doi: 10.1590/1519-6984.246062. eCollection 2021.
• Ali S, Mumtaz S, Shakir HA, Khan M, Tahir HM, Mumtaz S, Mughal TA, Hassan A, Kazmi SAR, Sadia, Irfan M, Khan MA. Current status of beta-thalassemia and its treatment strategies. Mol Genet Genomic Med. 2021 Dec;9(12):e1788. doi: 10.1002/mgg3.1788. Epub 2021 Nov 5.
• Dever DP, Bak RO, Reinisch A, Camarena J, Washington G, Nicolas CE, Pavel-Dinu M, Saxena N, Wilkens AB, Mantri S, Uchida N, Hendel A, Narla A, Majeti R, Weinberg KI, Porteus MH. CRISPR/Cas9 beta-globin gene targeting in human haematopoietic stem cells. Nature. 2016 Nov 17;539(7629):384-389. doi: 10.1038/nature20134. Epub 2016 Nov 7.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: November 16, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: 2024217A01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Share IPD with 5th Medical Center ofA General Hospital
• IPD Sharing Time Frame: The start date is October 2024 and the end date is July 2029
• IPD Sharing Access Criteria: The sponsors and collaborators are able to access the IPD and supporting information, IPD relies on team collaboration , as well as continuous improvement in innovation and efficiency. Participants will share project information, including the project's objectives, statistical datas, and clinical study report.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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