Clinical Trial: AMD 3100 for Treatment of Myelokathexis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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.

Detailed Summary: 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.
Sponsor: University of Washington

Current Primary Outcome: Blood Neutrophil Counts. [ Time Frame: up to 14 days, depending on when subject reached peak response, i.e., the highest count after the stimulus (plerixafor) ]

Effectiveness of drug based on increases of blood neutrophil counts to greater than 2.0 x 10^9 per liter


Original Primary Outcome: Blood neutrophil counts. The drug will be deemed effective if it increases the blood neutrophil count to a level greater than 2.0 x 10 9/L. Efficacy for the trial will be the percentage of patients achieving this level of blood neutrophils. [ Time Frame: The time frame for the increase in blood neutrophils will be up to 24 hours ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Washington

Dates:
Date Received: January 27, 2010
Date Started: October 2010
Date Completion:
Last Updated: May 16, 2012
Last Verified: May 2012