AMD 3100 for Treatment of Myelokathexis

NCT ID: NCT01058993

Last Updated: 2012-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2011-04-30

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.

Conditions

Neutropenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AMD3100 or plerixafor

SINGLE arm study with increasing doses of Plerixafor

Group Type: EXPERIMENTAL

AMD3100 or plerixafor

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Mozobil

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

David Dale

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David C Dale, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington Medical Center

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21835955 (View on PubMed)

Other Identifiers

MAMO-0407-1

Identifier Type: OTHER

Identifier Source: secondary_id

35419-D

Identifier Type: -

Identifier Source: org_study_id