Studies of the Immune Response to Vaccination After Hematopoietic Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01581164
First received: April 16, 2012
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

The purpose of this research study is to perform a serial analysis of immune function using blood cells and sera obtained from patients after vaccination following hematopoietic stem cell transplantation (HSCT). The focus of this study will be to characterize several immune parameters during the clinical course of HSCT and correlate these findings with the effect of vaccination.


Condition Intervention
Hematopoietic Stem Cell Transplant
Biological: Influenza vaccine
Biological: Varicella vaccine

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Studies of the Immune Response to Vaccination After Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Change from baseline of Immune response at Day 90 post vaccination. [ Time Frame: Participants will have blood drawn at baseline and on Days 1, 7, 10, 28, and 90 post vaccinations following hematopoietic stem cell transplantation. Average study participation is 1-3 years post transplant. ] [ Designated as safety issue: No ]
    Participants will have blood drawn at baseline to Day 90 post vaccinations following hematopoietic stem cell transplantation. Average study participation is 1-3 years post transplant.


Secondary Outcome Measures:
  • Immune response [ Time Frame: Participants will have blood drawn at 1 month intervals post hematopoietic stem cell transplantation . Average study participation is 1-3 years post transplant. ] [ Designated as safety issue: No ]
  • Immune response [ Time Frame: Blood will drawn at baseline and Days 1, 7, 10, 28, and 90 post vaccination. Participants will receive the vaccine, 12-28 months post hematopoietic stem cell transplantation. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum will be collected and stored for immunologic analysis after vaccination. Samples will be cryopreserved. No cell lines will be created using samples procured on this protocol.


Estimated Enrollment: 90
Study Start Date: December 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
HSCT patients
Patients who have been treated with HSCT
Biological: Influenza vaccine
Influenza vaccine: Injection, post transplant
Other Name: flu vaccine
Biological: Varicella vaccine
Varicella vaccine: Injection, post transplant
Other Name: chicken pox vaccine

Detailed Description:

Hematopoietic stem cell transplantation therapy is potentially curative for many malignant and non-malignant hematopoietic disorders. Disease recurrence and infection remain major causes of morbidity and mortality following HSCT. While innate immunity (myeloid and NK cell) is restored relatively quickly following HSCT, a prolonged period of lymphopenia occurs in all patients. This delay in lymphoid reconstitution is exacerbated with age and results in severely dampened adaptive immune responses. In children who have received chemotherapy and HSCT, T cell function generally recovers within 6 to twelve months. In contrast, lymphoid deficiency in adults may require years, and often never recovers to pre-transplant levels. Much of the delay in lymphocyte recovery is thought to be due to decreased thymic T cell production and export and the resulting expansion of treatment resistant T cell clones. Peripheral expansion of T cells in a lymphopenic setting leads to a narrowing of the TCR repertoire and manifests as a decrease in the magnitude of response to new antigens.

These long-lasting T cell deficiencies have been shown to play a direct role in post-transplant complications. There are many studies that correlate decreased T cell number and function (specifically CD4+ T cells) with an increase in post-transplant infections and relapse has been shown to be inversely proportional to T cell reconstitution following both autologous and allogeneic HSCT. Furthermore, this prolonged deficit in T cell function decreases the effectiveness of vaccination against tumour antigens and infectious diseases as well as other post-transplant immunotherapeutic strategies. Following HSCT, patients lose immunological memory not only to infectious microorganisms to which they were previously exposed but also bacterial and viral vaccines given prior to the HSCT , increasing the chance of infection post-transplant. Primary immunization requires antigenic stimulation and functionally mature T cells and therefore at least partial reconstitution of the T and B cell pools is necessary before successful reimmunization can occur.

This study presents an opportunity to analyze, at a systems level, the responses to vaccination in patients who are treated with HSCT. The expected high frequency of low responders to vaccination will permit comparisons of gene expression and immune cell activation between high and low responders as measured by the rate of seroconversion and HAI titers. The evaluation of live VZV vaccination is essential for these objective as the investigators hypothesize that live vaccination will induce a more specific immune response than dead (ie: influenza) vaccination. This study may also generate novel hypotheses about the mechanistic basis for reduced responses to vaccines post HSCT.

  Eligibility

Ages Eligible for Study:   5 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients who have been treated with HSCT

Criteria

Inclusion Criteria:

  • Patients who have been treated with HSCT.
  • Patients must be 5-70 years of age.
  • For patients participating in Objective 3: Patients must be immunocompetent (no active GVHD and must be off all immunosuppression)

Exclusion Criteria:

  • Patients who do not wish to participate or unable to provide the necessary blood samples required for the protocol.
  • Patients with history of allergic reaction to a vaccination.
  • Patient has had Guillain-Barre syndrome.
  • Patients who are pregnant or become pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01581164

Contacts
Contact: Jeffrey Venstrom, MD 415-353-2421

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Geraldine Pelle-Day    415-476-4765    gpelle-day@cc.ucsf.edu   
Contact: Karen McWhirter    415-476-8526    McWhirterK@cc.ucsf.edu   
Principal Investigator: Jeffrey Venstrom, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Jeffrey Venstrom, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01581164     History of Changes
Other Study ID Numbers: UCSF Protocol No. 112526
Study First Received: April 16, 2012
Last Updated: August 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
blood
hematopoietic
stem
cell
transplant
vaccine
vaccination
recovery
immune
system

ClinicalTrials.gov processed this record on September 30, 2014