Clinical trial NCT06734520: Clinical Study of Super Transplantation in the Treatment of Severe β-thalassemia
Official title: Clinical Study of Super Transplantation in the Treatment of Severe β-thalassemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Thalassemia Majors (Beta-Thalassemia Major)
Haplo-identical Donors
Lead sponsor: Guangzhou Women and Children's Medical Center
Sponsor class: OTHER
First posted: 2024-12-16
Enrollment: 3
Sex: ALL
Minimum age (years): 7
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: chimeric status
timeFrame: 1 year after transplantation.
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Guangzhou Medical University Affiliated Women's and Children's Medical Center
name: Hua Jiang, PHD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.