VZV Vaccine for Hematopoietic Stem Cell Transplantation

NCT ID: NCT02329457

Last Updated: 2019-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2019-10-31

Brief 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.

Conditions

Varicella Zoster Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

ID varicella zoster vaccine (VZVv) group

intradermal 0.65 mL Zostavax

Group Type: EXPERIMENTAL

Zostavax

Intervention Type: BIOLOGICAL

varicella zoster vaccine

SC VZVv group

subcutaneous 0.65 mL Zostavax

Group Type: ACTIVE_COMPARATOR

Zostavax

Intervention Type: BIOLOGICAL

varicella zoster vaccine

ID NS Group

intradermal 0.65 mL normal saline

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: BIOLOGICAL

normal saline placebo vaccine

SC NS Group

subcutaneous 0.65 mL normal saline

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: BIOLOGICAL

normal saline placebo vaccine

Interventions

Zostavax

varicella zoster vaccine

Intervention Type: BIOLOGICAL

Normal Saline

normal saline placebo vaccine

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• patients undergoing allogeneic hemopoietic stem cell transplant
• HLA identical sibling donors
• participants willing to provide written informed consents

Exclusion Criteria

• history of zoster in the 12 months prior to transplantation
• exposure to VZV within 4 weeks of transplantation
• neomycin sensitivity
• sensitivity to any components of the zoster vaccine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ivan FN Hung, MD FRCP

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Ivan Hung

Hong Kong, , Hong Kong

Countries

Hong Kong

References

Hata A, Asanuma H, Rinki M, Sharp M, Wong RM, Blume K, Arvin AM. Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants. N Engl J Med. 2002 Jul 4;347(1):26-34. doi: 10.1056/NEJMoa013441.

Reference Type: RESULT

PMID: 12097537 (View on PubMed)

Leung AY, Chow HC, Kwok JS, Lui CK, Cheng VC, Yuen KY, Lie AK, Liang R. Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007 Jun;39(11):661-5. doi: 10.1038/sj.bmt.1705673. Epub 2007 Apr 9.

Reference Type: RESULT

PMID: 17417658 (View on PubMed)

Other Identifiers

HKU 11-174

Identifier Type: -

Identifier Source: org_study_id