AMD 3100 for Treatment of Myelokathexis

NCT01058993 | Completed Phase 1 Results

• 2 other identifiers: 35419-DMAMO-0407-1
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Neutropenia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Blood Neutrophil Counts.

  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)

Study Arms (1)

AMD3100 or plerixafor

EXPERIMENTAL

SINGLE arm study with increasing doses of Plerixafor

Drug: AMD3100 or plerixafor

Interventions

AMD3100 or plerixafor 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.

Also known as: Mozobil

AMD3100 or plerixafor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• 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.

  PMID: 21835955 RESULT

MeSH Terms

Conditions

Neutropenia; WHIM syndrome

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Results Point of Contact

• Title: David D. Dale, MD
• Organization: University of Washington

dcdale@u.washington.edu

206-543-7215

Study Officials

• David C Dale, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 27, 2010
• First Posted: January 29, 2010
• Study Start: October 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: April 1, 2011
• Last Updated: June 15, 2012
• Results First Posted: June 15, 2012

Record last verified: 2012-05

Locations

US (1)