Base editing of blood stem cells and T cells to treat CD40L‑HyperIgM syndrome (single patient)
Official title: Base Editing Hematopoietic Stem Cell and BE T Cell Gene Therapy for CD40L-HyperIgM Syndrome-Single Patient Study
Run by National Institutes of Health Clinical Center (CC) · NCT06959771 · Data updated 2026-11-12
This treatment will try to repair the CD40L gene in a man's own blood stem cells and T cells using base editing to restore immune function in CD40L‑HyperIgM syndrome.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Ages | 37 Years to 120 Years |
| Sex | Men only |
| Enrollment | 1 (estimated) |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | alemtuzumab, chemotherapy |
| Locations | 1 site (Bethesda, Maryland) |
| Status | Recruiting |
| Started | July 16, 2025 |
| Main results expected | October 28, 2027 |
| Study ends | October 28, 2027 |
| Registry record updated | July 31, 2026 |
| Trial ID | NCT06959771 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
A single adult male with genetically confirmed CD40L c.658C>T; p.Q220X Hyper‑IgM syndrome who meets liver/hepatology clearance and can tolerate myeloablative conditioning is eligible.
✕Probably not a fit
People without the specific CD40L Q220X mutation, those unable to tolerate chemotherapy or with active uncontrolled infections or allergies to the cell products are unlikely to benefit.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This is a single-participant, first-in-human protocol delivering autologous base-edited hematopoietic stem/progenitor cells (HSPCs) followed by base-edited T cells to a man with the CD40L Q220X mutation. Prior to the HSPC infusion the participant receives myeloid conditioning with busulfan and serotherapy with alemtuzumab, and edited T cells are given two weeks later to accelerate T-cell recovery. The program aims to repair the disease-causing CD40L mutation ex vivo and return corrected cells to the patient as a one-time HSPC infusion with additional T-cell doses as needed. The participant will be monitored closely with visits every few months for the first two years and annual long-term follow-up thereafter.
Why it matters
Potential benefit: If successful, the approach could restore CD40L expression and durable immune function, reducing severe infections and autoimmune complications.
How similar studies have gone: Autologous HSPC gene therapies have restored immune function in other monogenic immunodeficiencies, but application of base editing to CD40L is largely novel with limited human data to date.
Who can join: the full rules
Show full inclusion / exclusion criteria
* 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 EXCLUSION CRITERIA: 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).
Where it's running
-
National Institutes of Health Clinical Center
Bethesda, Maryland, United States Recruiting
Study contacts
- Principal investigator: Suk S De Ravin, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
- Study coordinator: Suk S De Ravin, M.D.
- Email: sderavin@niaid.nih.gov
- Phone: (301) 496-6772
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.