Base Editing Hematopoietic Stem Cell and T Cell Gene Therapy for CD40L-HyperIgM Syndrome: Single Patient Study
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 participants
Jul 16, 2025
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria11
- 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
Exclusion Criteria6
- 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-0213. 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).
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Interventions
The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.
Serotherapy agent, 10 mg/m\^2 on days -21, -20 and -19
Immunophilin drug, will start on day -1, targeting a trough level between 4-12 ng/mL.
Mucositis prophylaxis agent, will be administered at 60 mcg/kg/day for 3 days before initiation of busulfan (days -6 to -4), as well as for the 3 days following study agent administration (days 1 to 3).
Myeloid conditioning agent, administered once daily (3 mg/kg) x 2 days, targeting a daily AUC of 4500 micromol\*min/L or a cumulative AUC of 9000 micromol\*min/L for the 2 days of therapy, if levels are available
The secondary study cell product is base edited autologous which will be administered as a one-time infusion two weeks following the infusion of the base-edited autologous HSPCs.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06959771