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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01573182
Recruitment Status : Recruiting
First Posted : April 6, 2012
Last Update Posted : May 4, 2017
Information provided by (Responsible Party):
David Gottlieb, University of Sydney

Brief Summary:

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 measurement by polymerase chain reaction assay (PCR) at the time of stem cell donation.

Condition or disease Intervention/treatment Phase
Herpes Zoster Biological: Zostavax Phase 2

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 (herpes zoster (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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : April 2012
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shingles
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Donor
VZV seropositive donors 50 years and over will receive vaccination with a live attenuated herpes zoster vaccine (Zostavax) by the intramuscular (IM) route 4 to 6 weeks prior to stem cell harvesting..
Biological: Zostavax
VZV seropositive donors 50 years and over will receive vaccination with a live attenuated herpes zoster vaccine (Zostavax) by the IM route 4 to 6 weeks prior to stem cell harvesting.

Primary Outcome Measures :
  1. Percentage of transplant recipients with VZV specific T cell proliferation within the first 12 moths post-transplant. [ 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 Zostavax vaccinated donors ]
    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 :
  1. Donor VZV positivity by PCR and genotype and donor VZV specific T cell response to vaccination [ Time Frame: 4 to 6 weeks after vaccination ]
    Donor VZV positivity by PCR and VZV specific T cell proliferation will be assessed 4 to 6 weeks after vaccination.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 immunoglobulin G (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01573182

Contact: David Gottlieb

Australia, New South Wales
Westmead Hospital Recruiting
Sydney, New South Wales, Australia, 2145
Contact: David Gottlieb   
Principal Investigator: David Gottlieb         
Sponsors and Collaborators
University of Sydney
Principal Investigator: David Gottlieb Westmead Hospital

Responsible Party: David Gottlieb, Professor, University of Sydney Identifier: NCT01573182     History of Changes
Other Study ID Numbers: VADOVAR
First Posted: April 6, 2012    Key Record Dates
Last Update Posted: May 4, 2017
Last Verified: May 2017

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

Additional relevant MeSH terms:
Herpes Zoster
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Immunologic Factors
Physiological Effects of Drugs