VZV Vaccine for Hematopoietic Stem Cell Transplantation
Condition: Varicella Zoster Infection
MeSH terms: Herpes Zoster; Chickenpox; Varicella Zoster Virus Infection
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Hematopoietic stem cell transplantation (HSCT) is well-established therapy for patients with
      malignant hematological diseases. Varicella zoster virus (VZV) reactivation, clinically
      manifested as herpes zoster (HZ), is a major complication that affects up to 50% of patients.
      Most patients will require hospitalization. Despite treatment with high dose acyclovir,
      patients may develop severe complications including the disabling postherpetic neuralgia,
      corneal ulceration, viral dissemination and secondary bacterial infection. The median onset
      of infection is the fifth month following transplantation, with 91% of cases occurring within
      the first year. Direct vaccination of transplants recipients with subcutaneous
      live-attenuated VZVv before transplantation and up to one year after transplantation is
      contraindicated. A small prospective non-randomized study has demonstrated that subcutaneous
      vaccination for donors before HSCT may offer some protection against VZV reactivation in the
      recipients. Recently, dose-sparing influenza vaccine delivered via a novel intradermal
      microneedle has been shown to elicit a good immunogenic response in both healthy and elderly
      subjects. We sought to assess the efficacy and safety of the novel intradermal
      live-attenuated VZVv in sibling donors undergoing HSCT.
    

Detailed description: 
      Hematopoietic stem cell transplantation (HSCT) is well-established therapy for patients with
      malignant hematological diseases. Varicella zoster virus (VZV) reactivation, clinically
      manifested as herpes zoster (HZ), is a major complication that affects up to 50% of patients.
      Most patients will require hospitalization. Despite treatment with high dose acyclovir,
      patients may develop severe complications including the disabling postherpetic neuralgia,
      corneal ulceration, viral dissemination and secondary bacterial infection. The median onset
      of infection is the fifth month following transplantation, with 91% of cases occurring within
      the first year. Direct vaccination of transplants recipients with subcutaneous
      live-attenuated VZVv before transplantation and up to one year after transplantation is
      contraindicated. A small prospective non-randomized study has demonstrated that subcutaneous
      vaccination for donors before HSCT may offer some protection against VZV reactivation in the
      recipients. Recently, dose-sparing influenza vaccine delivered via a novel intradermal
      microneedle has been shown to elicit a good immunogenic response in both healthy and elderly
      subjects. We sought to assess the efficacy and safety of the novel intradermal
      live-attenuated VZVv in sibling donors undergoing HSCT.

      We plan to enroll 160 pairs of adult donors and patients who undergo allogeneic HLA matched
      sibling HSCT in this prospective randomized double-blind placebo-controlled trial over a
      period of 3 years. Enrolled donors and patients will be randomized into 4 groups: Group 1:
      intradermal full dose live-attenuated VZVv; Group 2: subcutaneous full dose live-attenuated
      VZVv; Group 3: intradermal 0.9% normal saline as control; Group 4: subcutaneous 0.9% normal
      saline as the second control

      All vaccines will be given to the donors within 28 days before HSCT. All intradermal vaccines
      will be given via a microneedle syringe. Both the investigators and participants will be
      blinded to the randomization process. The primary end point is the occurrence of HZ in the
      patients within 12 months of transplantation. The secondary end points are the safety and
      immunological response in the patients and donors.
    

Intervention name(s): Zostavax; Normal Saline
Intervention type(s): Biological; Biological
Intervention description(s): varicella zoster vaccine; normal saline placebo vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: double-blind, randomized, intradermal, VZVv, HSCT