AMD 3100 for Treatment of Myelokathexis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
David Dale, University of Washington
ClinicalTrials.gov Identifier:
NCT01058993
First received: January 27, 2010
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Neutropenia
Drug: AMD3100 or plerixafor
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    Effectiveness of drug based on increases of blood neutrophil counts to greater than 2.0 x 10^9 per liter


Enrollment: 6
Study Start Date: October 2010
Study Completion Date: April 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMD3100 or plerixafor
SINGLE arm study with increasing doses of Plerixafor
Drug: AMD3100 or plerixafor
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.
Other Name: Mozobil

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01058993

Locations
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: David C Dale, MD University of Washington
  More Information

Publications:
Responsible Party: David Dale, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01058993     History of Changes
Other Study ID Numbers: 35419-D, MAMO-0407-1
Study First Received: January 27, 2010
Results First Received: August 3, 2011
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
neutropenia
myelokathexis
WHIM syndrome
AMD 3100
plerixafor
Myelokathexis syndrome
Neutropenia due to mutations of CXCR-4

Additional relevant MeSH terms:
Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014