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

University of Sydney

Status and phase: Completed; Phase 2

Conditions: Herpes Zoster

Treatments: Biological: Zostavax

Study type: Interventional

Funder types: Other

Identifiers

NCT01573182

VADOVAR

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Donor

Experimental group

Description:

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..

Treatment:

Biological: Zostavax