Clinical trial NCT01573182: Herpes Zoster Vaccine for Bone Marrow Transplant Donors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Herpes Zoster
Keywords: Zostavax
Herpes Zoster
VZV vaccination
Allogeneic haemopoietic stem cell transplantation
Lead sponsor: University of Sydney
Sponsor class: OTHER
First posted: 2012-04-06
Enrollment: 8
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Eligibility 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 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

Primary outcomes:
measure: Percentage of transplant recipients with VZV specific T cell proliferation within the first 12 moths post-transplant.
timeFrame: 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 outcomes:
measure: Donor VZV positivity by PCR and genotype and donor VZV specific T cell response to vaccination
timeFrame: 4 to 6 weeks after vaccination
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
affiliation: Westmead Hospital
name: David Gottlieb
role: PRINCIPAL_INVESTIGATOR
References: