Pneumonia Vaccine in Bone Marrow Transplant Recipients: Usefulness of Donor Vaccination

Immunogenicity of Pneumococcal Conjugate Vaccine in Adult Allogeneic Bone Marrow Transplant Recipients - Randomized Controlled Trial of Pre-Transplant Donor Immunization

Streptococcus pneumoniae, also known as Pneumococcus, is a common cause of pneumonia in transplant patients. There has been a vaccine available for this infection called Pneumovax. Recently, a new vaccine for this infection called Prevnar has been developed which may be more effective. Vaccinating the bone marrow donor before transplant may boost the recipient's immune response to the vaccine after transplant. This study is done to compare how vaccinating the donor with one of the vaccines will affect the recipient's immune system response to the vaccine.

Study Overview

• Status: Completed
• Conditions: Bone Marrow Transplant
• Intervention / Treatment: Biological: The polysaccharide vaccine used is Pneumovax (Merck vaccines); Biological: The conjugate vaccine used is Prevnar (Wyeth-Ayerst vaccines)

Detailed Description

This is a randomized controlled trial designed to assess the immunogenicity of the new pneumococcal conjugate vaccine in a cohort of allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. This will be done by using an approach of pre-transplant donor immunization with post-transplant recipient immunization. Response will be compared with the standard 23-valent polysaccharide vaccine. It is hypothesized that the conjugate vaccine will provide an enhanced response in this group of immunosuppressed individuals who respond poorly to standard polysaccharide vaccines.

Specific objectives of this study are:

• To determine the antibody response to both vaccines via a measurement of total antibody response and by the opsonophagocytic assay. This assay has the advantage of assessing if patient antibody responses represent truly functional antibodies that display opsonic activity against pneumococcus and is likely better correlated with protective efficacy.
• To determine any acute adverse reactions of the conjugate vaccine in this population. Results of this trial will help lay the foundation for the development of a rationale and optimal pneumococcal vaccination strategy that would prevent significant morbidity in this patient population.

We hypothesize that pneumococcal conjugate vaccine, due to its T-cell dependent response will have greater immunogenicity and protective effect in an allo-HSCT population by using a donor immunization strategy.

• Study Type: Interventional
• Enrollment: 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Recipient - Adult male or female marrow recipients who fulfill the following criteria will be eligible for the study: a) Will undergo allogeneic-HSCT in 2-3 weeks.

b) No splenectomy c) Not currently receiving IVIG d) Able to provide written informed consent and comply with study protocol e) Age > 16

Donor - Adult male or female marrow donors who fulfill the following criteria will be eligible for the study:

1. Recipient of donor marrow agrees to participate in study.
2. No prior pneumococcal vaccination within the last 5 years
3. Not on immunosuppressive medication (eg., corticosteroids)
4. No history of immunosuppressive condition that may potentially impair vaccine response eg, systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis
5. No splenectomy
6. Able to provide written informed consent and comply with study protocol
7. Age > 16

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Immunogenicity of two vaccines via a determination of serotype specific capsular antibody formation and functional antibody formation from donor and recipient serum.

Secondary Outcome Measures

Outcome Measure
All patients will be called by telephone 24 hours after receiving vaccine to determine if any acute adverse events occurred. Any occurance of pneumococcal disease in recipients for one year post-transplant during the study period will be recorded.

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: The Physicians' Services Incorporated Foundation
• Investigators: Principal Investigator: Deepali Kumar, BSc, MSc, MD, FRCP(C), University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): July 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: August 31, 2005
• First Submitted That Met QC Criteria: August 31, 2005
• First Posted (Estimate): September 2, 2005

Study Record Updates

• Last Update Posted (Estimate): April 16, 2008
• Last Update Submitted That Met QC Criteria: April 15, 2008
• Last Verified: August 1, 2005

More Information

Terms related to this study

• Keywords: Pneumonia; Vaccine; Bone Marrow Transplant; Conjugate Vaccine; Polysaccharide Vaccine
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 02-0182-C; P.S.I. Grant No. 02-67