Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM

Summary

Background:

Warts, hypogammaglobulinemia, infections and myelokathexis syndrome (WHIMs) is a rare disorder that affects the immune system. People with WHIMs can have severe infections all over their body. WHIMs is caused by a mutation in the CXCR4 gene. Treatment with drugs can help control the infections but does not cure the disorder. Researchers want to try a treatment where they collect stem cells from a person with WHIMS, use base-editing to replace the bad gene with a healthy version, and return the new cells to the person. This could cure WHIMs.

Objective:

To test a treatment using base-edited stem cells in people with WHIMs.

Eligibility:

People aged 3 years and older with WHIMs.

Design:

The study has 4 stages.

Stage 1: Screening. Participants will be screened at 1 or more visits. They will have a physical exam with blood tests. A sample of tissue and fluid (biopsy) will be taken from the bone marrow in the hip.

Stage 2: Apheresis. Blood will be taken from the body through a needle; the blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing.

Stage 3: Treatment. Participants will stay in the hospital for about 4 weeks. They will receive 3 drugs to prepare their body for the procedure. Then the edited stem cells will be returned to their bloodstream. They will stay in the hospital until they recover.

Stage 4: Follow-up. Participants will have 8 follow-up visits over 5 years. Long-term visits will continue for 15 years.

Conditions

• WHIM
• Warts
• Hypogammaglobulinemia
• Immunodeficiency
• Myelokathexis

Interventions

DRUG

Busulfan

Myeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol\*min/L.

DRUG

Palifermin

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).

DRUG

Plerixafor

Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.

DRUG

Filgrastim

Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.

BIOLOGICAL

Base-edited hematopoietic stem and progenitor cells

The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Suk S De Ravin, M.D. · National Institute of Allergy and Infectious Diseases (NIAID)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-26

Primary Completion

2031-12-31

Completion

2033-12-31

FDA Drug

Yes

Countries

• United States

Study Locations