Herpes Zoster Vaccine for Bone Marrow Transplant Donors (VZV-Zostavax)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
South West Sydney Local Health District
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
David Gottlieb, University of Sydney
ClinicalTrials.gov Identifier:
NCT01573182
First received: March 29, 2012
Last updated: April 4, 2012
Last verified: April 2012
  Purpose

The purpose of this study is to determine whether vaccination of stem cell donors with Zostavax can reduce the rate of Herpes Zoster reactivations in transplant recipients.

The clinical hypotheses is: 1) that Zostavax given to stem cell donors will induce protective VZV specific T cell proliferation in allogeneic stem cell transplant recipients that can be transferred to recipients; 2) and that donor vaccination with Zostavax is safe for transplant recipients as measured by viral load measurment by PCR at the time of stem cell donation.


Condition Intervention Phase
Herpes Zoster
Biological: Zostavax
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II Clinical Trial of Vaccination of Stem Cell Donors With Zostavax to Reduce the Incidence of Herpes Zoster in Transplant Recipients - A Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Sydney:

Primary Outcome Measures:
  • Percentage of transplant recipients with VZV specific T cell proliferation within the first 12 moths post-tranplant. [ Time Frame: incidence of VZV specific T cell proliferation in the first 12 months post allogeneic stem cell transplant in recipients receiving stem cells from Varivax vaccinated donors ] [ Designated as safety issue: No ]
    VZV specific T cell proliferation will be assessed at 3, 6, 9 and 12 months post transplant in stem cell transplant recipients.


Secondary Outcome Measures:
  • Donor VZV positivity by PCR and genotype and donor VZV specific T cell response to vaccination [ Time Frame: 4 to 6 weeks after vaccination ] [ Designated as safety issue: Yes ]
    Donor VZV positivity by PCR and VZV specific T cell proliferation will be assessed 4 to 6 weeks after vaccination.


Estimated Enrollment: 40
Study Start Date: April 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Donor
VZV seropositive donors 50 years and over.
Biological: Zostavax
VZV seropositive donors 50 years and over will receive vaccination with a live attenuated herpes zoster vaccine by the IM route 4 to 6 weeks prior to stem cell harvesting.

Detailed Description:

Infection is a major cause of morbidity and death among haemopoietic stem cell transplantation patients (HSCTs). Beyond the initial post-transplant (BMT) phase of neutropenia, the most common infections are cytomegalovirus (CMV) and fungal infections. Another common infection for which BMT patients are at increased risk is varicella-zoster virus (VZV) (both primary varicella and herpes zoster). VZV infection is controlled by specific T cell responses that are impaired post stem cell transplant.

Heat inactivated VZV vaccine has been shown to more than halve the incidence of herpes zoster in adult BMT patients undergoing autologous transplantation. Clinical protection was correlated with in vitro CD4 T-cell proliferation in response to varicella-zoster virus. Being a live vaccine, attenuated VZV and HZ vaccines are contraindicated within 24 months after allogeneic HSCT. However, priming of donor T-cells with herpes zoster vaccine may be a feasible alternative. One possible complication is the transfer of live virus from vaccinated donors to immunocompromised stem cell transplant recipients.

Normal donors donating for HLA matched siblings will be vaccinated with the Varivax vaccine prior to donation. Stem cell products will be assessed at the time of donation for evidence of VZV by PCR and for response to vaccination by T cell proliferation. Transfer of VZV proliferative responses in transplant recipients will be assessed by VZV specific T cell proliferation at 3, 6, 9 and 12 months post transplantation.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Allogeneic HSCT Recipient-donor pair
  • Donor aged 50 years and over
  • Recipients and donors willing to be recruited as a pair to this study
  • Recipients undergoing myeloablative or non myeloablative non T cell depleted, allogeneic stem cell transplants from HLA identical or 1 HLA antigen mismatched siblings.

Exclusion Criteria:

  • Lack of informed consent
  • Inability to recruit donor and recipient as a pair
  • Autologous transplant
  • Contraindication to Zostavax in donor
  • Donor aged <50 years
  • Recipient VZV IgG negative pre-transplantation,
  • Donor VZV IgG negative
  • Pregnancy of donor at randomisation
  • Inability to follow study protocol (donor and recipient)
  • Malignancy or immunosuppression of HSC donor
  • Expected HSCT within 30 to 42 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01573182

Locations
Australia, New South Wales
Westmead Hospital
Sydney, New South Wales, Australia, 2145
Sponsors and Collaborators
University of Sydney
South West Sydney Local Health District
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David Gottlieb Westmead Hospital
  More Information

No publications provided

Responsible Party: David Gottlieb, Professor, University of Sydney
ClinicalTrials.gov Identifier: NCT01573182     History of Changes
Other Study ID Numbers: VADOVAR
Study First Received: March 29, 2012
Last Updated: April 4, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Institutional Review Board

Keywords provided by University of Sydney:
Zostavax
Herpes Zoster
VZV vaccination
Allogeneic haemopoietic stem cell transplantation

Additional relevant MeSH terms:
Herpes Zoster
Herpesviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on April 17, 2014