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

May 3, 2018 updated by: David Gottlieb, University of Sydney

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2145
        • Westmead Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 to 6 weeks after vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sydney

Investigators

  • Principal Investigator: David Gottlieb, Westmead Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

May 3, 2018

Study Completion (Actual)

May 3, 2018

Study Registration Dates

First Submitted

March 29, 2012

First Submitted That Met QC Criteria

April 4, 2012

First Posted (Estimate)

April 6, 2012

Study Record Updates

Last Update Posted (Actual)

May 11, 2018

Last Update Submitted That Met QC Criteria

May 3, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VADOVAR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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