Base Editing Hematopoietic Stem Cell and BE T Cell Gene Therapy for CD40L-HyperIgM Syndrome-Single Patient Study

National Institute of Allergy and Infectious Diseases (NIAID)1 个研究点分布在 1 个国家目标入组 1 人开始时间: 2025年7月16日最近更新: 2026年7月31日

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: National Institute of Allergy and Infectious Diseases (NIAID)
入组人数: 1
试验地点: 1
主要终点: Safety determined by toxicities related to the infusion of the Study Cell Products

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Background:

X-linked hyper-IgM (HIGM) syndrome is caused by a mutation in the CD40 ligand (CD40L) gene. People with this disease have white blood cells that do not work properly. These people are at risk of severe infections and autoimmune diseases. Researchers want to know if these base-edited stem cells and T cells can help people with CD40L-HIGM syndrome.

Objective:

To test base-edited stem cells and base-edited T cells in 1 person with CD40L-HIGM syndrome.

Eligibility:

A single male with CD40L-HIGM syndrome.

Design:

A single participant is planned to receive a single dose of edited stem cells and supportive treatment with edited T cells. Participant stem and T cells will undergo base editing to repair the mutation.

In preparation for the gene therapy, the participant will receive busulfan chemotherapy and alemtuzumab. After treatment, the participant will have follow-up visits every few months in the first 2 years after treatment. Long-term visits will continue annually for 15 years.

详细描述

Study Description:

This is a single participant gene therapy study to provide a participant with CD40L c.658C>T; p.Q220X-Hyper IgM syndrome with autologous base-edited hematopoietic stem/progenitor cells (HSPC) and base-edited T cells (BE T). The study hypothesis is that base edited HSPCs will be repaired efficiently and safely to restore CD40L expression and improve immune function long term. BE T cells will provide functional T cells to support subject against immunodeficiency and lymphopenia.

The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan administered once daily for 2 days with a daily target AUC of 4500 micromol*min/L or a cumulative AUC of 9000 micromol*min/L (approximately 6 mg/kg) and serotherapy (alemtuzumab (Campath)) 10 mg/m^2 total dose divided over 3 days by subcutaneous injection on days -21, -20, and -19. Following infusion, the participant will be evaluated at months 3, 6, 9, 12, 18, 24. Long-term annual follow up will be performed on a separate protocol.

Base edited autologous T cells will be administered at 2 weeks following BE HSPC infusion that function as 'donor lymphocyte infusions' to protect the patient from the diseaserelated T-cell immunodeficiency and alemtuzumab-related lymphopenia. Subsequent doses of BE T cells may be infused monthly as indicated to achieve T cell reconstitution for treatment of infections.

Objectives:

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 37 Years 至 120 Years（Adult, Older Adult）
性别: Male
接受健康志愿者: 否

入选标准

•INCLUSION CRITERIA:
•This study is a single participant research study and to receive the study product, he needs to meet the following criteria:
•Provision of signed and dated informed consent form
•Stated willingness to comply with all study procedures and availability for the duration of the study
•Has CD40L Q220X mutation
•Defective class switching
•Liver abnormalities (transaminases>UL)
•Portal hypertension
•Consensus from Hepatology Consult to receive myeloid conditioning
•Ability to take oral medication and be willing to adhere to the intervention regimen
•Use of condoms or other methods to ensure effective contraception with partner
•Ability of subject to understand and the willingness to sign a written informed consent document

排除标准

•An individual who meets any of the following criteria will be excluded from participation in this study:
•Known allergic reactions to components of the BE HSPC study product or BE T cell product
•Febrile illness within two weeks of hospital admission for treatment
•Unwilling to submit their information as part of the alemtuzumab (Campath(R)) Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.
•NOTE: Alemtuzumab (campath) (IV formulation) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore no transplant will occur on this protocol. http://www.campath.com/
•Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies and NIH protocols 94-I-0073 and 05-I-
•Consideration for coenrollment in trials evaluating the use of a licensed medication will require the approval of the principal investigator in consultation with the medical monitor. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the principal investigator (in consultation with the medical monitor).