AMD 3100 for Treatment of Myelokathexis

Study Overview
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Brief Summary
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This is an initial study to determine if CXCR4 inhibitor AMD 3100 or plerixafor may be a potential treatment for neutropenia due to CXCR4 mutations, the myelokathexis or WHIM (warts, hypogammaglobulinemia, immunodeficiency and myelokathexis) syndrome. This is the initial study of this concept and will involve up to 6 patients to receive increasing doses of plerixafor administered subcutaneously or on an alternate day basis. It is unknown if these patients will be highly sensitive to a blockade of CXCR4 activity and release more white blood cells than normal volunteers or cancer patients given the same dose of this drug. Therefore doses will begin at a level 12 fold less than currently used to mobilize stem cells and will be increased stepwise to achieve an acceptable circulating level of neutrophils.

Detailed Description
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This is an open label, single Center, phase I study to examine the hematological effects, pharmacokinetics and safety of plerixafor in patients with myelokathexis attributable to mutations of CXCR4, utilizing serial, escalating doses of plerixafor administered on days 1, 3, 5, 8, and 10. Five intrapatient escalating dose levels, 20 micrograms per kilogram (mcg/kg), 40 micrograms/kilogram(mcg/kg), 80 micrograms/kilogram(mcg/kg), and 240 micrograms/kilogram (mcg/kg)will be examined. The subjects will be patients at the University of Washington General Clinical Research Center for up to 10 days; the study requires subject be available for up to 14 days. Patients will be monitored for hematological effects of plerixafor and observed for adverse effects. If a normal blood neutrophil count is achieved and maintained for at least 24 hours prior to the highest dose, we will stop at that level.

Official Title
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A Phase I Study of the CXCR-4 Inhibitor AMD3100 for the Treatment of Neutropenia Due to Mutations of CXCR-4, the Myelokathexis Syndrome

Conditions
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Neutropenia

Intervention / Treatment
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* Drug: AMD3100 or plerixafor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 years, WBC (white blood count) less than 3.0 x 10^9 per Liter, Absolute neutrophil count less than 2.0 x 10^9 per Liter, platelets greater than 100 x 10^6 per Liter, creatinine less than 2.0/milligrams per/deciliter, Creatinine clearance > 60 ml/min calculated, Aspartate Aminotransferase-GOT (SGOT), Alanin Aminotransferase-GPT (SGPT), bilirubin < 2.5 upper limit of normal, Eastern Cooperative Oncology Group (ECOG) status 0 or 1, mutation identified and confirmed in CXCR4, on no granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF) within 3 weeks of the study drug patient signs consent, accepts contraception Exclusion Criteria: greater than 18 years of age, sensitivity to plerixafor, pregnant, prisoner, decisionally impaired, judged unlikely to comply, illness that may interfere with interpretation of results, leukemia, malignancy, active infection requiring antibiotics within one week of study drug administration, history of cardiac conduction or electrocardiogram (EKG) abnormality, previous experimental therapy within one week.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMD3100 or plerixafor<br>SINGLE arm study with increasing doses of Plerixafor | Drug: AMD3100 or plerixafor<br>* The study will examine the hematological effects/safety of plerixafor in patients with myelokathexis attributable to mutations of CXCR4. Plerixafor will be administered on days 1, 3, 5, 8, and 10. Five intrapatient escalating doses of AMD 3100, 20 micrograms per kilogram (mcg/kg), 40 micrograms per kilogram (mcg/kg), 80 micrograms per kilogram (mcg/kg), and 240 micrograms per kilogram (mcg/kg) will be examined in the patients at University of Washington General Clinical Research Center for up to 10 days, requiring subjects be available up to 14 days. Patients will be monitored for hematological effects of plerixafor and observed for adverse effects. If normal blood neutrophil count is achieved and maintained for at least 24 hours prior to highest dose, we will stop at that level.<br>* Other names: Mozobil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Neutrophil Counts. | Effectiveness of drug based on increases of blood neutrophil counts to greater than 2.0 x 10^9 per liter | up to 14 days, depending on when subject reached peak response, i.e., the highest count after the stimulus (plerixafor) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neutropenia, myelokathexis, WHIM syndrome, AMD 3100, plerixafor, Myelokathexis syndrome, Neutropenia due to mutations of CXCR-4