A Phase 2/3 interventional study of Plerixafor and G-CSF in Myelokathexis, Infections and Neutropenia, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 10 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-06-26.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2/3, Interventional, and Treatment
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:
Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency disorder caused by gain-of-function mutations in the gene for the chemokine receptor CXCR4. Normally, CXCR4 is expressed on most leukocyte subsets and functions in part to promote hematopoietic stem cell (HSC) and neutrophil homing to and retention in bone marrow. WHIM mutations alter the CXCR4 carboxyl terminus, which enhances and prolongs receptor signaling. As a result, egress of normally produced and functional neutrophils from the bone marrow to the blood is impaired causing neutropenia, a bone marrow pathologic finding referred to as myelokathexis. A similar mechanism may also affect other leukocyte subsets since WHIM patients usually are panleukopenic. Consequently, WHIM patients are predisposed to frequent acute bacterial infections, especially in the sinopulmonary tract, that may cause chronic morbidity, respiratory insufficiency and in some cases premature death. WHIM patients also have marked difficulty clearing infections with Human Papillomavirus (HPV), resulting in persistent cutaneous and anogenital warts that in several reported cases have evolved into cancer. Several deaths have also occurred due to cancer associated with Epstein -Barr virus (EBV) infection. Therapies currently used for WHIMS are non-specific and expensive, and include Granulocyte Colony-Stimulating Factor (G-CSF) (the drug currently approved by the Food and Drug Administration (FDA) to treat severe congenital neutropenia), intravenous immunoglobulin (IVIg), and prophylactic antibiotics. None of these measures has been formally evaluated for efficacy in WHIM syndrome (WHIMS); however, in our clinical experience based on the treatment of 24 WHIM patients seen at the National Institutes of Health (NIH) since 2006, recurrent bacterial infections continue to occur, despite the fact that the absolute neutrophil count (ANC) can be readily maintained above 500 cells/microliter by G-CSF and IgG levels can be restored to the normal range by IVIg. Thus, there continues to be a major unmet medical need for effective therapy in WHIMS despite the availability and application of best therapy for neutropenia and hypogammaglobulinemia in these patients. Plerixafor (Mozobil ) is a specific small molecule antagonist of CXCR4, licensed by the FDA for HSC mobilization for transplantation in cancer, and is therefore a logical candidate for molecularly targeted treatment of WHIMS. The goal of treatment would be to reduce CXCR4 signaling to normal, not to zero, thus, absent any off-target effects, targeted chronic treatment with this agent may be safe. In this regard, 2 recent short term Phase I dose-escalation studies of plerixafor, one from our group, in a total of 9 patients demonstrated that the drug could safely mobilize not only neutrophils, but also all other leukocyte subsets that are decreased in the blood of WHIM patients. A follow-up Phase I study, conducted by our group, in 3 patients given plerixafor 0.02-0.04 mg/kg/d for 6 months demonstrated that these hematopoietic effects were durable. Moreover, the frequency of infection was reduced on plerixafor as compared to retrospective data mined for the three years before starting therapy and prospective data collected for one year after ending therapy, even though 2 of the patients were taking GCSF during the comparison time periods. No new warts occurred during treatment and several existing warts improved or resolved. Although these results are encouraging, the small number of patients studied, limited duration of drug treatment, and retrospective mining of control data leave open to question whether plerixafor is truly efficacious for clinical outcomes in WHIMS. The randomized, double blinded, crossover trial described here is designed to answer this question by establishing the long-term safety and clinical efficacy (primary endpoint: infection severity; multiple secondary endpoints including wart control) of plerixafor as compared to G-CSF in the treatment of WHIMS patients 10-75 years of age. G-CSF as a comparator is required because of its approved use in patients with severe congenital neutropenia (SCN).
Brief outline of study we intend to randomize 20 patients and treat them in a double-blinded manner for 1 year with G-CSF and 1 year with plerixafor using a crossover design to allow direct comparison of infection severity during treatment with both agents, at doses determined by the patient s individual neutrophil response. A schedule of events has been provided in Appendix A. Data will be analyzed as specified in the Statistics section (Section 14) after randomization. Tolerability and patient drug preference will also be assessed.
171 studies on the registry are indexed under Warts; 35 are open to participants now.
This study's enrollment of 20 is below the median of 70 across 155 interventional studies indexed under Warts.
Browse Warts studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Compared within Warts, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Infections. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Subjects are eligible to enter the study if they meet all of the following criteria:
All study subjects must agree not to become pregnant or impregnate a female. Women of 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 , one of which must be a barrier method, and must continue contraception until 5 months after stopping the study drug:
EXCLUSION CRITERIA:
If any of the following exclusion criteria are met, a subject will not be enrolled in this study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Study drugs were both given subcutaneously twice daily for 14 months using unmarked prefilled glass syringes
Drug: Plerixafor · Drug: G-CSF
Study drugs were both given subcutaneously twice daily for 14 months using unmarked prefilled glass syringes
Drug: Plerixafor · Drug: G-CSF
Twice daily low dose injection for 14 months.
Also known as: Mozobil
Twice daily low dose injection for 14 months.
Also known as: Neupogen
Severity of Infection
The primary outcome is a Total Infection Severity Score (TISS). Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these scores were summed (weighted based on time at risk) to create a total infection severity score (TISS) in each period for each participant (range 0 to infinity). Drug failures during a period were pre-defined to count as more extreme than any TISS score. The primary analysis outcome is based on the Difference in Total Infection Severity Score (TISS) in Period 1 minus TISS in Period 2 analysis, with drug failures in only one period assigned the highest absolute value for the difference, with the sign defined according to the treatment order (e.g., negative for period 2 drug failures only). Higher values of the difference represent a worse outcome in the first period than in the second period. Thus, each participant's infection severity
Time frame: Scores from 12 months treatment on each study drug
Difference in Total Infection Severity Score
The primary outcome is a difference: the Total Infection Severity Score (TISS) in Period 1 minus the TISS in Period 2. Higher values represent a worse outcome in the first period than in the second period. Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these individual infection scores were summed (weighted by time at risk) to create a total infection severity score (TISS) in each period. Because there is no pre-determined number of infections, the range is -infinity to +infinity. If a participant has a drug failure in only one period, their difference rank is either the highest rank (if the failure is in Period 1) or the lowest rank (if the failure is in Period 2), failure on both periods gives a difference of 0. 1 subject failed on both treatments, and 3 subjects failed only on plerixafor.
Time frame: Scores from 12 months treatment on each study drug
1 subject could not tolerate minimal possible dose of G-CSF (Neupogen) 15 micrograms subcutaneously twice daily during screening period and was not randomized
| Milestone | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor |
|---|---|---|
| Started | 10 | 9 |
| Completed | 8 | 7 |
| Not completed | 2 | 2 |
| Withdrew: Adverse event | 2 | 1 |
| Withdrew: Lack of efficacy | 0 | 1 |
The primary outcome is a Total Infection Severity Score (TISS). Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these scores were summed (weighted based on time at risk) to create a total infection severity score (TISS) in each period for each participant (range 0 to infinity). Drug failures during a period were pre-defined to count as more extreme than any TISS score. The primary analysis outcome is based on the Difference in Total Infection Severity Score (TISS) in Period 1 minus TISS in Period 2 analysis, with drug failures in only one period assigned the highest absolute value for the difference, with the sign defined according to the treatment order (e.g., negative for period 2 drug failures only). Higher values of the difference represent a worse outcome in the first period than in the second period. Thus, each participant's infection severity
| score on a scale (with no maximum) | G-CSF (Both Periods Combined) | Plerixafor (Both Periods Combined) |
|---|---|---|
| Severity of Infection | 12.5 (0 to 36) | 9 (0 to 24) |
The primary outcome is a difference: the Total Infection Severity Score (TISS) in Period 1 minus the TISS in Period 2. Higher values represent a worse outcome in the first period than in the second period. Each infection during the 12 month period of treatment on each drug was scored for severity on a scale of 1-10 with higher scores representing more severe infections and then these individual infection scores were summed (weighted by time at risk) to create a total infection severity score (TISS) in each period. Because there is no pre-determined number of infections, the range is -infinity to +infinity. If a participant has a drug failure in only one period, their difference rank is either the highest rank (if the failure is in Period 1) or the lowest rank (if the failure is in Period 2), failure on both periods gives a difference of 0. 1 subject failed on both treatments, and 3 subjects failed only on plerixafor.
| score on a scale | Plerixafor in Period 1 and G-CSF in Period 2 | G-CSF in Period 1 and Plerixafor in Period 2 |
|---|---|---|
| Difference in Total Infection Severity Score | 10.6 (1 to 19) | 9.33 (1 to 19) |
Collected over up to 14 months on each study drug. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| G-CSF | 0/19 (0%) | 6/19 (31.6%) | 19/19 (100%) |
| Plerixafor | 0/19 (0%) | 2/19 (10.5%) | 19/19 (100%) |
| Event | G-CSF | Plerixafor |
|---|---|---|
| Flu-like illnessInfections and infestations | 1/19 | 0/19 |
| ArthritisMusculoskeletal and connective tissue disorders | 1/19 | 1/19 |
| pneumoniaInfections and infestations | 1/19 | 0/19 |
| Urinary tract infectionInfections and infestations | 1/19 | 0/19 |
| AppendicitisInfections and infestations | 1/19 | 0/19 |
| CellulitisInfections and infestations | 0/19 | 1/19 |
| Transient ischemic attackNervous system disorders | 1/19 | 0/19 |
| Event | G-CSF | Plerixafor |
|---|---|---|
| Bone painMusculoskeletal and connective tissue disorders | 14/19 | 7/19 |
| Acute bronchitisInfections and infestations | 9/19 | 2/19 |
| NauseaGastrointestinal disorders | 6/19 | 1/19 |
| Upper Respiratory Tract InfectionInfections and infestations | 5/19 | 6/19 |
| Otitis mediaInfections and infestations | 6/19 | 1/19 |
| GastroenteritisInfections and infestations | 6/19 | 0/19 |
| HeadacheNervous system disorders | 6/19 | 3/19 |
| Weight gainInvestigations | 2/19 | 5/19 |
| Knee painMusculoskeletal and connective tissue disorders | 5/19 | 2/19 |
| Urinary Tract InfectionInfections and infestations | 4/19 | 2/19 |
| Age, Categorical(Participants) | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor | Total |
|---|---|---|---|
| <=18 years | 1 | 4 | 5 |
| Between 18 and 65 years | 9 | 5 | 14 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor | Total |
|---|---|---|---|
| Female | 8 | 5 | 13 |
| Male | 2 | 4 | 6 |
| Race (NIH/OMB)(Participants) | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 8 | 7 | 15 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Plerixafor First Then Filgrastim | Filgrastim First Then Plerixafor | Total |
|---|---|---|---|
| United States | 8 | 7 | 15 |
| El Salvador | 1 | 0 | 1 |
| Sweden | 1 | 0 | 1 |
| Spain | 0 | 2 | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2014 to primary completion in Oct 2020, 71 months.
Results were first posted in Apr 2023, 2 years 5 months after primary completion.
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Studies of the drugs tested here: Plerixafor · Granulocyte Colony-Stimulating Factor
National Institute of Allergy and Infectious Diseases (NIAID) →