Gardasil Vaccination in Post Stem Cell Transplant Patients
Condition: Gardasil Vaccine; Stem Cell Transplant; Immunogenicity
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Gardasil , a recently approved vaccine for the sexually transmitted human papillomavirus
           (HPV), provides immunity to four types of HPV that are associated with genital warts and
           cervical, vaginal, and vulvar precancer and cancer. The vaccine has been shown to be
           highly effective in preventing infection with these HPV types and was approved for use
           by the Food and Drug Administration.

        -  More research is needed about the vaccine s ability to induce immunity in individuals
           with suppressed immune systems, such as those who have had other kinds of cancer
           treatment such as stem cell transplant. Genital warts, precancer, and cancer have been
           reported as a late complication after stem cell transplant. Researchers are interested
           in determining whether the HPV vaccine is safe to give and able to induce immunity in
           female stem cell transplant recipients, their female donors, and healthy female
           volunteers.

      Objectives:

      - To assess the safety and immune response of the HPV vaccine in female recipients of stem
      cell transplants who are either off or on stable doses of immunosuppression.

      Eligibility:

        -  Females between 18 and 50 years of age who have had allogenic stem cell transplants.

        -  Healthy female volunteers, including stem cell donors, are also eligible for this study.

      Design:

        -  Participants will be screened with a physical examination, blood and urine tests, and
           saliva samples, and will be asked to complete a sexual quality of life questionnaire.

        -  Sexually active participants will also have a routine gynecologic evaluation.

        -  Participants will receive three HPV vaccinations according to the standard vaccination
           schedule (with the second and third following 2 and 6 months after the first).
           Participants will record their daily temperature and any reactions to the vaccine on a
           vaccine report card for 1 week after each vaccination.

        -  Participants will have clinic visits for further testing 2, 6, 7, and 12 months after
           receiving the first HPV vaccine.
    

Detailed description: 
      HPV associated genital dysplasia is a complication following hematopoietic allogeneic stem
      cell transplantation (HSCT). In a recent study from this institution, one third of female
      transplant recipients had HPV related genital tract dysplasia. The quadrivalent human
      papillomavirus virus (HPV) (types 6, 11, 16, 18) vaccine (Gardasil ) is now approved for use
      in females aged 9-26 for the prevention of cervical cancer and, more recently, vulvar and
      vaginal cancer. In this study, Gardasil will be used in females age 18 years to 50 at least
      90 days post stem cell transplant in two study cohorts to determine its safety and
      immunogenicity in this population, as a first step to reduce post-transplant HPV-related
      co-morbidity, genital dysplasia and malignancy. The two study cohorts will both be post
      transplant; one off of immunosuppression (n=24), and one on immunosuppression (n=24).
      Gardasil will be administered using the FDA approved regimen of 3 separate 0.5ml
      intramuscular injections at 0, 2, and 6 months. The primary objectives of this study are to
      determine the safety and immunogenicity of Gardasil in female allogeneic HSCT recipients. A
      cohort of healthy subjects will also be vaccinated (n=24) and will serve as a control.
      Immunogenicity studies characterizing the CD4 and CD8 T- cell response, change in antibody
      titer and cytokine response from baseline to months seven and twelve will be compared in the
      three cohorts. Additionally, genital exams will be performed to monitor for HPV. Secondary
      endpoints will characterize sexual function post-transplant and vulvar/vaginal
      graft-versus-host disease (GVHD). When available, healthy female stem cell donors
      corresponding to enrolled vaccine recipients will be enrolled (n=10) as part of the healthy
      cohort and vaccinated to determine whether there are differences in HPV vaccine
      immunogenicity in a subset of donors and their respective allogeneic, HSCT female recipients.

      As stem cell transplant becomes more applicable to the general population with newer
      transplant techniques allowing for a larger donor pool and as survival improves, problems
      associated with long term survivorship such as genital dysplasia, will become more prevalent.
      Vaccine therapy to prevent or eradicate this disease is needed.
    

Intervention name(s): Gardasil
Intervention type(s): Biological
Intervention description(s): 3 separate 0.5 ml intramuscular
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Women's Health; Genital Precancer; Stem Cell Donor; Cervical Cytology; Healthy Volunteers; Stem Cell Transplant; Healthy Volunteer; HV