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

Conditions

• CD40L-HyperIgM Syndrome

Eligibility Criteria

Sex

MALE

Age

37 Years - 120 Years

Healthy Volunteers

Not accepted

Interventions

• Base-edited hematopoietic stem and progenitor cells — BIOLOGICAL
  The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.
• Alemtuzumab — DRUG
  Serotherapy agent, 10 mg/m\^2 on days -21, -20 and -19
• Sirolimus — DRUG
  Immunophilin drug, will start on day -1, targeting a trough level between 4-12 ng/mL.
• Palifermin — DRUG
  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).
• Busulfan — DRUG
  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
• Base-edited T lymphocyte cells — BIOLOGICAL
  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.

Study Details

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.

Key Dates

Start date

Jul 16, 2025

Status verified

Mar 2026

Primary completion

Oct 28, 2027

Completion

Oct 28, 2027

Study Design

Enrollment

1 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Single Arm Study
  The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following conditioning using busulfan and alemtuzumab.

Primary Outcome Measure

Safety determined by toxicities related to the infusion of the Study Cell Products [ Time Frame: Through end of study ]

Central Contacts

• Suk S De Ravin, M.D.
  (301) 496-6772
  [email protected]

Locations (1)

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