Gardasil Vaccination in Post Stem Cell Transplant Patients

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Gardasil Vaccine, Stem Cell Transplant, Immunogenicity

Intervention / Treatment
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* Biological: Gardasil


Participation Criteria
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Eligibility Criteria
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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) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1<br>Female subjects post stem cell transplant on no systemic immunosuppression. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. | Biological: Gardasil<br>* 3 separate 0.5 ml intramuscular<br>|
| Active Comparator: Cohort 2<br>Female subjects post stem cell transplant with chronic GVHD requiring systemic immunosuppression. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. | Biological: Gardasil<br>* 3 separate 0.5 ml intramuscular<br>|
| Active Comparator: Cohort 3<br>Healthy normal female volunteers. Gardasil® will be administered using the FDA approved regimen of 3 separate 0.5ml intramuscular injections at 0, 2, and 6 months. | Biological: Gardasil<br>* 3 separate 0.5 ml intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Developed Antibody Response to the Vaccine. | The percentage of subjects who developed antibody response to the quadrivalent HPV (qHPV) vaccine (HPV - 6/ - 11/ - 16/ - 18). Anti-HPV-6/11/16/18-specific antibody responses using L1 Virus Like Particle (VLP) ELISA were measured in serum. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Women's Health, Genital Precancer, Stem Cell Donor, Cervical Cytology, Healthy Volunteers, Stem Cell Transplant, Healthy Volunteer, HV