Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome

Background: \- WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is a rare disease. It can cause cancers, infections, and warts. Researchers want to see if a drug called plerixafor can treat WHIMS. Objective: \- To compare plerixafor versus granulocyte colony stimulating factor (G-CSF) for preventing infections in people with WHIMS. Eligibility: \- People ages 10-75 with WHIMS who have a CXCR4 gene mutation. Design: * Participants will be screened with a medical history, physical exam, and blood and urine tests. They may have heart and spleen tests and body scans. They may have samples of skin or warts taken. Researchers may take photographs of warts. * Participants will start twice daily self-injections of G-CSF. Their doctors will decide the dosage. * Initial Period (4-12 weeks) * Participants will: * continue the injections and their usual antibiotics and/or immunoglobulin * have blood drawn * keep a daily health diary * Participants will visit the clinic for 2 days without injections. * Adjustment Period 1 (8 weeks): * Participants will: * continue twice daily injections from home * continue the daily health diary * have blood tests every 2 weeks. * Treatment Year 1: * Participants will * receive either plerixafor or G-CSF injections twice daily * continue the health diary * have blood tests every 2 months * visit the clinic about every 4 months * At the end of year 1, participants will visit the clinic for an evaluation. They will switch to the other study drug. They will have an 8-week adjustment and 1-year treatment period. * At the end of year 2, participants will visit the clinic to complete their injections and go back to their previous G-CSF regimen. Participants will continue their daily health diary and have blood tests for 5-6 months.

Sex

All

Minimum age

10 Years

Maximum age

75 Years

* INCLUSION CRITERIA:

Subjects are eligible to enter the study if they meet all of the following criteria:

1. Age greater than or equal to 10 and less than or equal to 75 years.
2. Heterozygous mutation in the C-tail of CXCR4 in addition to a clinical diagnosis of WHIMS.
3. Documented neutropenia with a baseline ANC below 1500 cells/microL of blood.
4. History of severe and/or recurrent infections.
5. Willingness to interrupt G-CSF medication, 2 days prior to study drug injection.
6. Must have a local medical provider for medical management.
7. Must be willing to provide blood, plasma, serum, and DNA samples for storage.
8. All study subjects must agree not to become pregnant or impregnate a female. Women of childbearing potential must agree to take appropriate steps to avoid becoming pregnant for the duration of the study. Participants in whom pregnancy is biologically possible must use at least 2 study approved methods of contraception, one of which must be a barrier method, and must continue contraception until 5 months after stopping the study drug:

   * Male or female condoms with a spermicide,
   * Diaphragm or cervical cap with spermicide,
   * Intrauterine device,
   * Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive,
   * Male partner with vasectomy and documented aspermatogenic sterility.
9. Willingness to comply with the study medications, visits, and procedures, as deemed necessary by the principal investigator (PI).

EXCLUSION CRITERIA:

If any of the following exclusion criteria are met, a subject will not be enrolled in this study:

1. Neutropenia due to maturation defects in the myeloid lineage or a type of neutropenia, which in the investigator s opinion, is unlikely to improve from the medication administered in this study.
2. Pregnant or breast-feeding women.
3. Known hypersensitivity to plerixafor, G-CSF, or any components of the products.
4. Predisposition to or history of life-threatening cardiac arrhythmia.
5. Requiring dialysis or having markedly impaired renal function with a Creatinine Clearance (CrCl) \<15 mL/min.
6. Condition that in the investigator s opinion places a subject at undue risk by participating in the study.

• RESULTMcDermott DH, Velez D, Cho E, Cowen EW, DiGiovanna JJ, Pastrana DV, Buck CB, Calvo KR, Gardner PJ, Rosenzweig SD, Stratton P, Merideth MA, Kim HJ, Brewer C, Katz JD, Kuhns DB, Malech HL, Follmann D, Fay MP, Murphy PM. A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome. J Clin Invest. 2023 Oct 2;133(19):e164918. doi: 10.1172/JCI164918. PMID 37561579
• DERIVEDZalewski CK, Kim HJ, Brewer CC, Martinez S, Rieger C, Cho E, McDermott DH, Murphy PM. The Audiologic and Otolaryngologic Phenotype in WHIM Syndrome. Otolaryngol Head Neck Surg. 2026 Aug 17. doi: 10.1002/ohn.70396. Online ahead of print. PMID 42606118