Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM
Phase 1/2 Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM
2 other identifiers
interventional
10
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2026
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 19, 2026
CompletedFirst Posted
Study publicly available on registry
August 20, 2026
CompletedStudy Start
First participant enrolled
October 7, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2031
Study Completion
Last participant's last visit for all outcomes
December 31, 2033
October 2, 2026
September 15, 2026
5.2 years
August 19, 2026
October 1, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To evaluate the safety of base-edited autologous CD34+ cells
Safety of gene therapy using base-edited autologous hematopoietic stem and progenitor cells as measured by study agent-related adverse events and serious adverse events
Initiated from the time of the infusion of base-edited cells through 2 years post-infusion
Secondary Outcomes (4)
Evaluate the efficacy of base-edited autologous CD34+ cells
Assessed 12 months post-infusion of base-edited cells
Evaluate genetic correction
Assessed 12 months post-infusion of base edited cells
Evaluate immune reconstitution
Assessed 12 months post-infusion of base edited cells
Evaluate clinical efficacy
Assessed 12 months post-infusion of base edited cells
Study Arms (1)
Single arm study
EXPERIMENTALThe study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan.
Interventions
Myeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol\*min/L.
Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.
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).
The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.
Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.
Eligibility Criteria
You may qualify if:
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Aged \>= 3 years and weighing \>=15 kg.
- Confirmed CXCR c.1000C\>T, pR334X mutation.
- Ability to undergo apheresis for stem cell collection.
- Medical lab data (historical) of neutropenia, or B cell dysfunction (low or absent IgG levels, or on IV gamma globulin.
- Expected survival of at least 120 days.
- Must be willing to have blood and tissue samples stored.
- Participants of reproductive potential must agree to consistently use effective contraception from start of busulfan conditioning through at least one-year post-treatment. Acceptable forms of contraception are:
- Hormonal contraception in continuously effective use.
- Male or female condom with spermicide as indicated.
- Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide.
- Intrauterine device in-situ
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Acute onset infection as indicated by symptoms such as persistent fevers, or imaging (new pneumonia on CT for example), isolated pathogen and requiring medical intervention.
- Severe liver dysfunction with transaminases \> 6 fold upper limit will be excluded until approval by hepatology consult who will provide mitigating plans for liver protection.
- Renal dysfunction-serum creatinine \>3.0 x ULN.
- Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time \>2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).
- Known hypersensitivity to busulfan or any component of the product.
- Contraindications for administration of busulfan, including but not limited to: hypersensitivity, chronic lymphocytic leukemia, acute leukemia in blastic crisis, pregnancy, or lactation.
- Childhood malignancy (occurring before 18 years of age) in the participant or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer unless approved by the with appropriate consultants and approved by the study PI (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol).
- Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the participant, or would preclude the participant from successful study completion.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Suk S De Ravin, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 19, 2026
First Posted
August 20, 2026
Study Start (Estimated)
October 7, 2026
Primary Completion (Estimated)
December 31, 2031
Study Completion (Estimated)
December 31, 2033
Last Updated
October 2, 2026
Record last verified: 2026-09-15