AMD 3100 for Treatment of Myelokathexis

May 16, 2012 updated by: David Dale, University of Washington

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Mozobil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
up to 14 days, depending on when subject reached peak response, i.e., the highest count after the stimulus (plerixafor)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Investigators

  • Principal Investigator: David C Dale, MD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

January 27, 2010

First Submitted That Met QC Criteria

January 28, 2010

First Posted (Estimate)

January 29, 2010

Study Record Updates

Last Update Posted (Estimate)

June 15, 2012

Last Update Submitted That Met QC Criteria

May 16, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 35419-D
  • MAMO-0407-1 (Other Identifier: Protocol ID #)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neutropenia

Clinical Trials on AMD3100 or plerixafor

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cyprus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe