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AMD 3100 for Treatment of Myelokathexis

Primary Purpose

Neutropenia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AMD3100 or plerixafor

About this trial

This is an interventional treatment trial for Neutropenia focused on measuring neutropenia, myelokathexis, WHIM syndrome, AMD 3100, plerixafor, Myelokathexis syndrome, Neutropenia due to mutations of CXCR-4

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Washington Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AMD3100 or plerixafor

Arm Description

SINGLE arm study with increasing doses of Plerixafor

Outcomes

Primary Outcome Measures

Blood Neutrophil Counts.

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

Secondary Outcome Measures

Full Information

NCT ID

NCT01058993

First Posted

January 27, 2010

Last Updated

May 16, 2012

Sponsor

University of Washington

1. Study Identification

Unique Protocol Identification Number

NCT01058993

Brief Title

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

2. Study Status

Record Verification Date

May 2012

Overall Recruitment Status

Completed

Study Start Date

October 2010 (undefined)

Primary Completion Date

March 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Washington

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neutropenia

Keywords

neutropenia, myelokathexis, WHIM syndrome, AMD 3100, plerixafor, Myelokathexis syndrome, Neutropenia due to mutations of CXCR-4

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AMD3100 or plerixafor

Arm Type

Experimental

Arm Description

SINGLE arm study with increasing doses of Plerixafor

Intervention Type

Drug

Intervention Name(s)

AMD3100 or plerixafor

Other Intervention Name(s)

Mozobil

Intervention Description

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.

Primary Outcome Measure Information:

Title

Blood Neutrophil Counts.

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David C Dale, MD

Organizational Affiliation

University of Washington

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Washington Medical Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21835955

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.

Results Reference

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AMD 3100 for Treatment of Myelokathexis

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