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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01092195
Recruitment Status : Completed
First Posted : March 24, 2010
Last Update Posted : March 19, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:


  • 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.


- 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.


  • 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.


  • 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 or disease Intervention/treatment Phase
Gardasil Vaccine Stem Cell Transplant Immunogenicity Biological: Gardasil Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : March 18, 2010
Actual Primary Completion Date : July 19, 2016
Actual Study Completion Date : July 19, 2016

Intervention Details:
  • Biological: Gardasil
    3 separete 0.5 ml intramuscular

Primary Outcome Measures :
  1. Difference between HPV titers at pre-vaccine baseline and HPV titers at 7 and 12 mo, respectively, after first vaccination for each of the four sub-types 6, 11, 16 and 18. Safety will be captured using the CTCAE Version 4. [ Time Frame: 7, 12 months ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. To characterize sexual function in post stem cell transplant recipients compared to healthy age-matched women [ Time Frame: 1,7,12 months ]
  5. To characterize genital graft versus host disease (GVHD) in the stem cell transplant population [ Time Frame: 1, 12 months ]
  6. 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 ]
  7. To characterize cell mediated immunity among the different groups of HSCT recipients and healthy, normal donors [ Time Frame: 1,2,6,7,12 months ]
  8. To characterize the HPV subtypes carried in these different populations [ Time Frame: 1,7,12 months ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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


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


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


Healthy female subject

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


Vaccine Recipient:

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01092195

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Minocher M Battiwalla, M.D. National Heart, Lung, and Blood Institute (NHLBI)