A Phase I Trial of Safety and Immunogenicity of Gardasil Vaccination Post Stem Cell Transplantation in Patients With and Without Immunosuppression

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier:
NCT01092195
First received: March 23, 2010
Last updated: September 26, 2014
Last verified: September 2014
  Purpose

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.

Condition Intervention Phase
Gardasil Vaccine
Stem Cell Transplant
Immunogenicity
Biological: Gardasil
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Safety and Immunogenicity of Gardasil Vaccination Post Stem Cell Transplantation in Patients With and Without Immunosuppression

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary endpoint is the difference between HPV titers at pre-vaccine baseline and HPV titers at 7 and 12 months, respectively, after first vaccination for each of the four sub-types 6, 11, 16 and 18. Safety will be captured using the CTCAE... [ Time Frame: 7, 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine if there is a difference in immune response to vaccination in patients on or off of immunosuppression [ Time Frame: 1,2,6,7,12 months ] [ Designated as safety issue: No ]
  • To determine if there is a difference in immune response to HPV vaccine compared to the immune response mounted to other vaccines in a subset of allogeneic HSCT female recipients who are being revaccinated as part of routine care. [ Time Frame: 1,2,6,7,12 months ] [ Designated as safety issue: No ]
  • To determine whether there are differences in HPV vaccine immunogenicity in a subset of female donors and their respective allogeneic HSCT female recipients [ Time Frame: 1,2,6,7,12 months ] [ Designated as safety issue: No ]
  • To characterize sexual function in post stem cell transplant recipients compared to healthy age-matched women [ Time Frame: 1,7,12 months ] [ Designated as safety issue: No ]
  • To characterize genital graft versus host disease (GVHD) in the stem cell transplant population [ Time Frame: 1, 12 months ] [ Designated as safety issue: No ]
  • To test the correlation of HPV vaccine immunogenicity among the four HPV subtypes in the quadrivalent vaccine [ Time Frame: 1,2,6,7,12 months ] [ Designated as safety issue: No ]
  • To characterize cell mediated immunity among the different groups of HSCT recipients and healthy, normal donors [ Time Frame: 1,2,6,7,12 months ] [ Designated as safety issue: No ]
  • To characterize the HPV subtypes carried in these different populations [ Time Frame: 1,7,12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: March 2010
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Gardasil
    3 separete 0.5 ml intramuscular
Detailed Description:

HPV associated genital dysplasia is a complication following hematopoetic 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 e) 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 e will be used in females age 18 years to 50 at least 90 days post stem cell transplant with full donor chimerism in two study cohorts to determine its safety and immunogenicity in this population, as a first step to reduce posttransplant 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). Gardasile will be administered using the FDA approved regimen of 3 separate O.Sml 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 .

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Female stem cell transplant recipient at least 90 days post stem cell transplant

OR

Female stem cell transplant recipient at least 90 days post HSCT and on immunosuppression

OR

The matched female stem cell transplant donor for an included stem cell transplant recipient

OR

Healthy female subject

Age greater than or equal to 18 years and less than or equal to 50 years

EXCLUSION CRITERIA:

Vaccine Recipient:

Obvious HPV condyloma or obvious severe dysplasia (greater than or equal to CIN II)

History of severe adverse reaction to any components (yeast, eggs, monosodium glutamate or neomycin) of the quadrivalent HPV vaccine.

Untreated or persistent life-threatening infections not controlled by current treatment

Uncontrolled chronic GVHD i.e. highly active eGVHD requiring immediate intervention

Pregnant or breast feeding or unwilling to be abstinent or practice effective contraception during the study period (note: patients who have been rendered infertile with total body irradiation are eligible)

Enrollment in another vaccine clinical trial during the study period

Enrollment of healthy volunteer in a drug clinical trial during the study period

Inability to comprehend the investigational nature of the study and provide informed consent< TAB>

Prior Gardasil or other HPV vaccination

Persistent or recurrent malignancy

  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: NCT01092195

Contacts
Contact: Pamela Stratton, M.D. (301) 496-9079 strattop@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Pamela Stratton, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT01092195     History of Changes
Other Study ID Numbers: 100083, 10-CH-0083
Study First Received: March 23, 2010
Last Updated: September 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Women's Health
Genital Precancer
Stem Cell Donor
Cervical Cytology
Healthy Volunteers
Stem Cell Transplant
Healthy Volunteer
HV

ClinicalTrials.gov processed this record on October 22, 2014