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.
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
- 21 Oct 2026to 31 Dec 2033
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
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.
Read more
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 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.
- First posted20 Aug 2026
- Study start21 Oct 2026
- 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)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Suk S De Ravin, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
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
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Base-Edited Hematopoietic Stem/Progenitor Cell Gene Therapy for Treatment of CXCR4-WHIM
- ClinicalTrials.gov ID
- NCT07775313
- Acronym / sponsor ID
- 10002691
- Conditions
- WHIM, Warts, Hypogammaglobulinemia, Immunodeficiency, Myelokathexis
- Keywords
- Gene Editing, base editing
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 21 Oct 2026 (actual)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2033 (estimated)
- First posted
- 20 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm study | Experimental | Drug: Busulfan, Drug: Palifermin, Drug: Plerixafor, Drug: Filgrastim, Biological: Base-edited hematopoietic stem and progenitor cellsThe study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan. |
Who may qualify
- Ages
- 3 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BusulfanMyeloid conditioning agent, administered once daily x 2 days, targeting a total AUC of 9000 micromol*min/L. | Drug | Single arm study |
| PaliferminMucositis 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 | Single arm study |
| PlerixaforHematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product. | Drug | Single arm study |
| FilgrastimHematopoietic stem cell mobilizing agent necessary for the collection of the hematopoietic stem and progenitor cells (HSPCs) to create the study product. | Drug | Single arm study |
| Base-edited hematopoietic stem and progenitor cellsThe study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning. | Biological | Single arm study |
Primary outcome
To evaluate the safety of base-edited autologous CD34+ cells
Time frame: Initiated from the time of the infusion of base-edited cells through 2 years post-infusion
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
4 secondary outcomes
Evaluate the efficacy of base-edited autologous CD34+ cells
Time frame: Assessed 12 months post-infusion of base-edited cells
Evaluate genetic correction
Time frame: Assessed 12 months post-infusion of base edited cells
Evaluate immune reconstitution
Time frame: Assessed 12 months post-infusion of base edited cells
Evaluate clinical efficacy
Time frame: Assessed 12 months post-infusion of base edited cells
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Suk S De Ravin, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety of base-edited autologous CD34+ cells (time frame: Initiated from the time of the infusion of base-edited cells through 2 years post-infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.