AMD 3100 for Treatment of Myelokathexis
Condition: Neutropenia
MeSH terms: Neutropenia
Intervention: AMD3100 or plerixafor
Intervention description: 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.
Intervention MeSH terms: Plerixafor
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: neutropenia; myelokathexis; WHIM syndrome; AMD 3100; plerixafor; Myelokathexis syndrome; Neutropenia due to mutations of CXCR-4

Summary:

      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.
    

Eligibility criteria:

        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.