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A Phase I Study of Mozobil (TM) in the Treatment of Patients With WHIMS

Phase 1
18 Years
75 Years
Open (Enrolling)
WHIMS, Neutrophil Disorder, Myelokathexis, Hypogammaglobulinemia

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Trial Information

A Phase I Study of Mozobil (TM) in the Treatment of Patients With WHIMS

Mozobil (TM) (plerixafor injection, Genzyme Corp.) is a Food and Drug Administration
approved medication to mobilize CD34+ hematopoietic stem cells prior to apheresis and use in
autologous transplantation in non-Hodgkin lymphoma and multiple myeloma when used in
conjunction with granulocyte-colony stimulating factor (G-CSF). The drug's mechanism of
action is the specific and reversible inhibition of the chemokine receptor, CXCR4, expressed
on CD34+ cells and other leukocytes. This inhibition interferes with the binding of stromal
cell derived factor-1 (SDF-1), which is constitutively expressed on bone marrow stromal
cells and appears to cause direct and indirect cellular adhesive interactions. Severe
congenital neutropenia is a rare inherited disorder in which the affected individuals
develop chronic or cyclical neutropenia with circulating counts below 500 cells/microliter
blood. This disorder may result from a variety of genetic defects in progenitor- or
neutrophil-expressed genes such as elastase, CXCR4, G6PC3, etc. Myelokathexis is the
abnormal retention of mature leukocytes in the bone marrow and is seen in some types of
severe chronic neutropenia such as warts, hypogammaglobulinemia, infections, and
myelokathexis syndrome (WHIMS). WHIMS is a rare primary immunodeficiency, which is known to
be caused by mutations that enhance CXCR4 signaling. Our hypothesis is that Mozobil(TM) can
be used safely to partially block CXCR4 and treat neutropenia resulting from myelokathexis
at doses considerably lower than that being used for CD34+ cell mobilization. This new
treatment could also improve other aspects of the disease such as frequent infections,
warts, and hypogammaglobulinemia. To test this hypothesis, we propose this Phase I trial of
Mozobil (TM) in adults with WHIMS, examining safety and absolute neutrophil count as the
primary endpoint.

Inclusion Criteria


All of the following inclusion criteria must be met for a subject to be enrolled in this

- Clinical diagnosis of WHIMS and documented severe infection

- Must be greater than or equal to 18 and less than or equal to 75 years of age

- Willingness to interrupt medications to raise the white count (WBC) such as G-CSF or
GM-CSF for at least 1 week before and while on the study drug

- Willingness to interrupt treatment with intravenous immunoglobulins (IVIG) while on
the study drug.

- Must not be pregnant or breastfeeding

- Must have a personal physician

- Must be willing to provide blood, plasma, serum, and DNA samples for storage

- Subjects must agree not to become pregnant or to impregnate a female. If of
childbearing potential, must agree to consistently use two types of contraception
throughout study participation. Acceptable forms of contraception include the

1. Condoms, male or female, with or without a spermicide

2. Diaphragm or cervical cap with spermicide

3. Intrauterine device

4. Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved
contraceptive method

5. Male partner has previously undergone a vasectomy for which there is
documentation of aspermatogenic sterility


If any of the following exclusion criteria are met, a subject will not be enrolled in this

- Absence of a diagnosis of WHIMS

- Patient is less than 18 years old

- Absence of a documented history of severe infection

- Neutropenia due to maturation defects in the myeloid lineage or that the PI feels is
unlikely to benefit from this medication

- Pregnant women or breastfeeding

- History of hematopoietic origin cancer (lymphoma, leukemia, multiple myeloma, etc.)
or known chromosomal defects that could make such more likely

- History of serious cardiac arrhythmia or cardiac defects that make such more likely

- Renal failure (calculated creatinine clearance [CrCl] < 15 mL/min or requiring

- Signs or symptoms of active microbial infection

- Any condition that, in the investigator's opinion, places the patient at undue risk
by participating in the study

- Unwillingness to undergo testing or procedures associated

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine whether or not Mozobil (TM) is safe in study population.

Principal Investigator

David H McDermott, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Allergy and Infectious Diseases (NIAID)


United States: Federal Government

Study ID:




Start Date:

July 2009

Completion Date:

June 2014

Related Keywords:

  • Neutrophil Disorder
  • Myelokathexis
  • Hypogammaglobulinemia
  • WHIM
  • Mozobil (TM)
  • Neutrophil Disorder
  • Plerixafor
  • Agammaglobulinemia



National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892