Clinical trial NCT01058993: AMD 3100 for Treatment of Myelokathexis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neutropenia
Keywords: neutropenia
myelokathexis
WHIM syndrome
AMD 3100
plerixafor
Myelokathexis syndrome
Neutropenia due to mutations of CXCR-4
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2010-01-29
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 description: 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.

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.

Primary outcomes:
measure: Blood Neutrophil Counts.
timeFrame: up to 14 days, depending on when subject reached peak response, i.e., the highest count after the stimulus (plerixafor)
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: David C Dale, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dale DC, Bolyard AA, Kelley ML, Westrup EC, Makaryan V, Aprikyan A, Wood B, Hsu FJ. The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome. Blood. 2011 Nov 3;118(18):4963-6. doi: 10.1182/blood-2011-06-360586. Epub 2011 Aug 11.