Clinical Trial: Plerixafor Versus G-CSF in the Treatment of People With WHIM Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase III Double-Blind Randomized Crossover Study of Plerixafor Versus G-CSF in the Treatment of Patients With WHIM Syndrome.

Brief Summary:

Background:

- WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is a rare disease. It can cause cancers, infections, and warts. Researchers want to see if a drug called plerixafor can treat WHIMS.

Objective:

- To compare plerixafor versus granulocyte colony stimulating factor (G-CSF) for preventing infections in people with WHIMS.

Eligibility:

- People ages 10 75 with WHIMS who have a CXCR4 gene mutation.

Design:

  • Participants will be screened with a medical history, physical exam, and blood and urine tests. They may have heart and spleen tests and body scans. They may have samples of skin or warts taken. Researchers may take photographs of warts.
  • Participants will start twice daily self-injections of G-CSF. Their doctors will decide the dosage.
  • Initial Period (4 12 weeks)
  • Participants will:
  • continue the injections and their usual antibiotics and/or immunoglobulin
  • have blood drawn
  • keep a daily health diary
  • Participants will visit the clinic for 2 days without injections.
  • Adjustment Period 1 (8 weeks):
  • Participants will:
  • continue twice daily injections from home
  • continue the daily health diary
  • have blood tests

    Detailed Summary:

    Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIMS) is a rare combined primary immunodeficiency disorder caused by gain-of-function mutations in the gene for the chemokine receptor CXCR4. Normally, CXCR4 is expressed on most leukocyte subsets and functions in part to promote hematopoietic stem cell (HSC) and neutrophil homing to and retention in bone marrow. WHIM mutations alter the CXCR4 carboxyl terminus, which enhances and prolongs receptor signaling. As a result, egress of normally produced and functional neutrophils from the bone marrow to the blood is impaired causing neutropenia, a bone marrow pathologic finding referred to as myelokathexis. A similar mechanism may also affect other leukocyte subsets since WHIM patients usually are panleukopenic. Consequently, WHIM patients are predisposed to frequent acute bacterial infections, especially in the sinopulmonary tract, that may cause chronic morbidity, respiratory insufficiency and in some cases premature death. WHIM patients also have marked difficulty clearing infections with Human Papillomavirus (HPV), resulting in persistent cutaneous and anogenital warts that in several reported cases have evolved into cancer. Several deaths have also occurred due to cancer associated with Epstein -Barr virus (EBV) infection. Therapies currently used for WHIMS are non-specific and expensive, and include Granulocyte Colony-Stimulating Factor (G-CSF) (the drug currently approved by the Food and Drug Administration (FDA) to treat severe congenital neutropenia), intravenous immunoglobulin (IVIg), and prophylactic antibiotics. None of these measures has been formally evaluated for efficacy in WHIM syndrome (WHIMS); however, in our clinical experience based on the treatment of 24 WHIM patients seen at the National Institutes of Health (NIH) since 2006, recurrent bacterial infections continue to occur, despite the fact that the absolute neutrophil count (ANC)
    Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

    Current Primary Outcome: The primary endpoint is infection severity, which is measured as a composite of multiple weighted parameters according to rules defined in Appendix D of the protocol. [ Time Frame: Every 4 months ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Component measures of infections; incidence and duration of infections, fevers, antibiotic treatments, and hospitalization. [ Time Frame: 1 year ]
    • Control of warts as defined by at least a 50% reduction in numbers, areas or size of existing warts and number of new warts. [ Time Frame: 1 Year ]
    • Blood count and immunological parameters. [ Time Frame: Per Schedule of events ]


    Original Secondary Outcome: Same as current

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 3, 2014
    Date Started: August 27, 2014
    Date Completion: June 30, 2020
    Last Updated: April 20, 2017
    Last Verified: July 27, 2016