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Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Summary
Background: Chronic granulomatous disease (CGD) is a rare immune disorder caused by a mutation in the CYBB gene. People with CGD have white blood cells that do not work properly and are at greater risk of getting infections. Gene therapy using lentivector has helped people with CGD. Researchers want to know if the base-edited stem cells can improve the white cells' functioning and result in fewer CGD-related infections. Objective: To learn if base-edited stem cells will correct the white blood cells in people with CGD. Eligibility: Males aged 18 years and older with X-linked CGD. Design: This is a non-randomized study. Participants with the specific mutation under study will be screened during the initial phase. During the development phase, participants will undergo apheresis to collect stem cells for base-editing correction of the mutation. During the treatment phase, participants will receive the base-edited cells after chemotherapy with busulfan. Participants will remain in the hospital until their immunity recovers. Participants will be maintained on sirolimus to prevent an immune response to the new protein expressed by the base-edited cells. Follow-up visits will continue for 15 years.
Official title: Phase 1/2 Trial of Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-linked Chronic Granulomatous Disease
Key Details
Gender
MALE
Age Range
18 Years - 75 Years
Study Type
INTERVENTIONAL
Enrollment
10
Start Date
2024-04-17
Completion Date
2032-12-31
Last Updated
2026-04-06
Healthy Volunteers
No
Interventions
Plerixafor
Stem Cell Mobilizing Agent: Subcutaneous administration for 2 consecutive days to improve stem cell collection.
Filgrastim
Stem Cell Mobilizing Agent: Subcutaneous administration for 6 consecutive days. It is necessary to mobilize stem cells for collection.
Palifermin
Mucositis Prophylaxis Agent: Intravenous infusion of keratinocyte growth factor (Palifermin) at 60 mcg/kg/day before (Days -7 to Day -5 administration of busulfan and (Days 1 to 3) post-busulfan administration to prevent oral mucositis.
Busulfan
Transplant Conditioning Agent: An alkylating chemotherapy drug to enhance engraftment of the study agent (base-edited stem cells). Conditioning will be given intravenously over 3 days with an approximate total dose of 12mg/kg. Drug levels obtained will be obtained to achieve the targeted total busulfan AUC of 65,000 ng/mL x hr.
Base-edited hematopoietic stem and progenitor cells
Investigational/Study Agent: Base-edited autologous CD34 plus hematopoietic stem and progenitor cell product. The product is administered intravenously as a single infusion. This product is under an IND.
Sirolimus
Immunomodulating agent: Daily oral dosing beginning Day -1 for approximately 3 to 6 months to prevent an immune response to the protein expressed by the BE HSPCs.
Locations (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, United States