WHIMPhase 1/2NCT07775313

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

A Phase 1/2 study testing Busulfan, Palifermin and Plerixafor in people with WHIM and Warts, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 3 to 75 years
Conditions the study is for: WHIM, Warts, Hypogammaglobulinemia
What is being tested?: Busulfan, Palifermin and Plerixafor
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteUnited States
Study dates: 28 Oct 2026to 31 Dec 2033
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 75 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

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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

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Phase 1/2 Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM

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.

Read the detailed description

Study Description:

This is a phase 1/2, non-randomized study of a single infusion of autologous hematopoietic stem/progenitor cells (HSPC) base-edited to repair CXCR4 mutations in 10 participants with (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) WHIM syndrome.

Primary Objective: Evaluate safety of treatment with BE-HSPC CXCR4 in participants with WHIM syndrome.

Secondary Objectives:

Evaluate:

Efficacy.
Genetic correction.
Immune reconstitution.
Clinical efficacy.

Exploratory Objective:

Evaluate off-target (OT) editing activity.

Primary Endpoint:

Safety assessed by:

Incidence of adverse events (AEs) for each participant.
Evaluate overall incidence of AEs for the study.
Incidence of serious adverse events (SAEs).

Secondary Endpoints (24 months post-study agent infusion):

Efficacy: >= 5% gene edited circulating myeloid cells by 12 months after BE HSPC infusion.
Gene correction: --Frequency of corrected alleles in peripheral blood cells (such as myeloid, T, B, and natural killer [NK] cells). -->200/microL edited neutrophils by 12 months post receipt of the BE HSPC infusion.
Immune reconstitution:
T, B, and NK cell number improvement from baseline.
B-cell function: immunoglobulin (Ig) production.
Clinical efficacy: Improvement from baseline problems such as recurrent infection, wart burden, gastrointestinal complaints, or immune dysregulation.

Exploratory Endpoint:

Evaluate for frequency of OTs by high-throughput sequencing (HTS) of the target mutation at the genomic locus 2 years post-infusion.

Conditions: WHIM, Warts, Hypogammaglobulinemia, Immunodeficiency, Myelokathexis
Being tested: Busulfan, Palifermin, Plerixafor, Filgrastim, Base-edited hematopoietic stem and progenitor cells
Keywords: Gene Editing, base editing
Medical subject headings: Warts, Agammaglobulinemia, Immunologic Deficiency Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BusulfanDrug
Myeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol*min/L.
PaliferminDrug
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).
PlerixaforDrug
Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.
FilgrastimDrug
Hematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product.
Base-edited hematopoietic stem and progenitor cellsBiological
The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning.

Study groups in NCT07775313
Study group	Role	What they receive
Single arm study	Experimental	The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan. Receives: Drug: Busulfan; Drug: Palifermin; Drug: Plerixafor; Drug: Filgrastim; Biological: Base-edited hematopoietic stem and progenitor cells

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Efficacy of gene therapy as determined by percentage of participants who have >= 5 percent gene edited circulating myeloid cells
Measured: Assessed 12 months post-infusion of base-edited cells
Evaluate genetic correction
Genetic correction as determined by the presence of >200/uL edited neutrophils
Measured: Assessed 12 months post-infusion of base edited cells
Evaluate immune reconstitution
Immune reconstitution as determined by: T, B, and NK cell number improvement from baseline; immunoglobulin production
Measured: Assessed 12 months post-infusion of base edited cells
Evaluate clinical efficacy
Clinical efficacy as determined by: improvement from baseline problems (i.e., recurrent infections, wart burden)
Measured: Assessed 12 months post-infusion of base edited cells

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Oct 202631 Dec 2033

First posted20 Aug 2026
Study start28 Oct 2026 (estimated)
Primary completion31 Dec 2031 (estimated)
Study completion31 Dec 2033 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for WHIMStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07775313
Sponsor's protocol ID: 10002691
Other IDs: 002691-I
Status last verified: 15 Sep 2026
First submitted: 19 Aug 2026
Last updated: 23 Oct 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided