Preventive Human Papillomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients
Study Details
Study Description
Brief Summary
This phase II trial studies whether the nonavalent human papillomavirus vaccine given to adults prior to kidney transplantation can help the body build and maintain an effective immune response during the post-transplant period when they receive immunosuppressive drugs to prevent transplant rejection. This study will help inform our scientific understanding about vaccine-induced immune responses among immunosuppressed individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- To assess human papillomavirus (HPV) vaccine-type-specific seroconversion rates at 12-months post-transplantation among kidney transplant recipients who receive >= 1 doses of the recombinant human papillomavirus nonavalent vaccine (Gardasil 9 HPV vaccine) >= 30 days prior to transplantation.
SECONDARY OBJECTIVES:
- To evaluate the following in adult kidney transplant recipients who receive >= 1 doses of the Gardasil 9 HPV vaccine prior to transplantation:
Ia. HPV vaccine-type-specific seroconversion rates at 12-months post-transplantation.
Ib. Persistence and stability of HPV vaccine-type-specific geometric mean titers (GMT) at 6 and 12-months post-transplantation, and rise in HPV vaccine-type-specific GMT at the 13 month post-transplant visit.
Ic. Vaccine safety profile and allograft rejection/opportunistic infections stratified by number of vaccine doses and time between the last vaccine dose and the transplant procedure.
Id. HPV detection in self-collected samples from the cervix/vagina, and oral cavity at baseline (pre-vaccination) and at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3), sexual behavior, type-specific seroconversion rates, and time elapsed between the last vaccine dose and the transplant procedure.
Ie. Descriptive analysis to explore differences or similarities between the genders from the secondary objective outcomes above.
OUTLINE:
Participants receive the first dose of the recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) at baseline, at least 30 days prior to the kidney transplant surgery. The second dose is given at least one month after the first dose. The third dose is given at least five months after the first dose and at least three months after the second dose. The timing of the second and third doses is dependent on the scheduling of the kidney transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or all three vaccine doses prior to the kidney transplant surgery, and are offered additional visits at least one year after the surgery to complete any remaining doses of the three-dose vaccine series.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Prevention (Gardasil 9 HPV vaccine) Participants receive the first dose of the recombinant human papillomavirus nonavalent vaccine IM at baseline, at least 30 days prior to the kidney transplant surgery. The second dose is given at least one month after the first dose. The third dose is given at least five months after the first dose and at least three months after the second dose. The timing of the second and third doses is dependent on the scheduling of the kidney transplant surgery. Patients are followed up at 6- and 12-months after the kidney transplant surgery to measure vaccine-induced immune responses. Patients may receive either one, two, or all three vaccine doses prior to the kidney transplant surgery, and are offered additional visits at least one year after the surgery to complete any remaining doses of the three-dose vaccine series. |
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Questionnaire Administration
Ancillary studies
Biological: Recombinant Human Papillomavirus Nonavalent Vaccine
Given IM
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Human papillomavirus (HPV) vaccine-type-specific seroconversion rates among kidney transplant recipients who receive >= 1 doses of the vaccine >= 30 days prior to transplantation [12 months post-transplant]
Will provide an estimate of the rate and two approximate and one exact 95% confidence intervals (CIs). For approximate CI will use a) approximate normality of p-hat, and b) approximate normality of log(p-hat); and for exact CI will use the Clopper-Pearson exact confidence interval.
Secondary Outcome Measures
- HPV vaccine-type-specific seroconversion rates [12 months post-transplant]
Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. Will compare stratified rates to each other, using an exact test for number doses. Will provide mean, median, and range for time elapsed for time elapsed for subgroups of interest between last vaccine dose and transplant procedure. Lists of dosing types by medication variety will be provided and summaries applied when possible and appropriate and interactions with type of transplant surgery (living donor/deceased donor) for variations in dosing and types of post-transplant immunosuppressant medications. Descriptive statistics and graphics will be used for visual comparison and assessment for differences in human leukocyte antigen histocompatibility between donor and recipient.
- Persistence and stability of HPV vaccine-type-specific geometric mean titers (GMT) [At 6 and 12 months post-transplant]
Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. Persistence will be measured as the difference in means between two times (6 and 12-months post-transplant) while stability will be assessed by measures of spread appropriate for the transformation at hand.
- Rise in HPV vaccine-type-specific GMT [13 months post-transplant]
Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI.
- Vaccine safety profile and allograft rejection/opportunistic infections [Up to 13 months post-transplant]
Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. Safety profile and injections will be listed, stratified by number of doses (1, 2, or 3) and time to transplant (long, short) and summarized as possible.
- HPV detection in samples from the cervix/vagina, and oral cavity [Self-collected at baseline (pre-vaccination) and at 6- and 12- months post-vaccination]
Will provide descriptive statistics such as means, rates, and exact or approximate 95% CI. HPV detection in samples from the cervix/vagina, and oral cavity at baseline (pre-vaccination) and at 6- and 12-months post-vaccination, overall and by number of vaccine doses (1, 2, or 3), sexual behavior, type-specific seroconversion rates, and time elapsed between the last vaccine dose and the transplant procedure will be evaluated. All rates of HPV detection will be specified, overall and stratified by number of doses (1, 2, or 3) and time to transplant.
- Differences and similarities between genders [Up to 12 months post-transplant]
A descriptive analysis will be performed to explore differences or similarities between genders from the secondary objective outcomes.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Candidate for renal transplant, expected to undergo transplant surgery >= 30 days and =< 12 months after enrollment
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For potential participants on the institutional waiting list for deceased donor transplant, a study clinician confirms the candidate is likely to receive a transplant within the next 12 months, taking into account the candidate's priority on the waiting list, age, medical status, institutional policies, and scores like the Estimated Post-Transplant Survival (EPTS) Score and Calculated Panel Reactive Antibody (CPRA) percentage, etc
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For potential participants expected to undergo a living donor transplant, one or more donor(s) have been identified and is/are in work-up (even though all work-up status may or may not be complete); a study clinician confirms the living donor transplant is likely to be scheduled within the next twelve months after taking into account donor work-up progress, age and medical status, and institutional policies
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Notes:
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Living and deceased donor transplant recipients: The study was originally restricted to participants who were expecting to receive only living donor renal transplants; however, less than a third of kidney transplants in the United States occur with kidneys from living donors; a majority of transplants are in the setting of donation of kidneys from deceased donors; to permit efficiencies in accrual, the study is amended (from version 3.5) to also open enrollment to recipients of deceased donor kidneys
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Transplant recipients of both genders: The study was originally designed to be conducted only among women; however, in October 2018, the Food and Drug Administration (FDA) approved an age expansion indication for the Gardasil 9 HPV vaccine for both women and men up to 45 years (from the originally approved upper age limit of 26 years), thus opening a new clinical cancer preventative option for middle-age adults of both genders; the primary endpoint for the study is HPV-vaccine-type-specific seroconversion rates, which are not expected to be differential by gender, based on extrapolating from the uniformly high (> 99%) seroconversion rates observed regardless of gender in studies among immunocompetent individuals; however, HPV vaccine-type-specific titer levels (geometric mean titre [GMT]) differences by gender will be analyzed as a secondary endpoint, given variability in immune response titer levels observed between males and females in immunocompetent individuals (related to the differences in body mass index or hitherto unproven factors related to hormone-immune interactions); another advantage of expanding this study to males will be to facilitate efficiencies in accrual, since men constitute the majority (55%-65%) of all kidney transplant recipients in the United States; although a majority of current HPV-associated cancers among solid organ transplant recipients occur among women, there is increasing evidence of the link between HPV infection and oropharyngeal cancers that disproportionately affect men; HPV-related oropharyngeal cancers are now the most common HPV-related cancers in the United States, surpassing even the incidence of cervical cancer; the expansion of enrollment to men will also allow this study to look at the effect of HPV vaccination on persistence of oral HPV infection as a secondary/exploratory endpoint in the context of transplant-related immunosuppression
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Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
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The effects of the Gardasil 9 HPV vaccine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because there have been no adequate and well-controlled studies of Gardasil 9 in pregnant women, women who are able to become pregnant must have a confirmed negative pregnancy test result within the past 28 days prior to enrollment and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; women who have had a both ovaries removed or a tubal ligation will not be required to have a pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
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Ability to understand and the willingness to sign a written informed consent document and medical release form
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Willing and able to comply with trial protocol and follow-up
Exclusion Criteria:
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Previous prophylactic HPV vaccination
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Prior organ transplant
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Anticipated desensitization treatment; this decision to exclude a participant who may need desensitization will be based on the site clinician's judgement; desensitization procedures vary somewhat among the five participating transplant centers, which does not permit proposing uniform criteria across all study sites for determining exclusion due to desensitization; in general, participants who have received a prior transplant, have unsuitable scores on Calculated Panel Reactive Antibody (PRA) percentage (institution-specific thresholds), or an ABO incompatible donor are likely to undergo desensitization at one or more of the study centers; these factors, among others, will be used by the study clinician to determine exclusion due to anticipated desensitization is warranted for a particular participant in the study
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Current use of any other investigational agents
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History of allergic reactions to yeast or attributed to compounds of similar chemical or biologic composition to Gardasil 9 HPV vaccine
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Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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For female participants: Pregnant or intention to get pregnant, or breastfeeding; pregnant women are excluded from this study because the safety and effectiveness of Gardasil 9 HPV vaccine have not been established in pregnant women; it is not known whether Gardasil 9 is excreted in human milk; because many drugs are excreted in human milk, caution should be exercised when Gardasil 9 is administered to a nursing woman; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Gardasil 9, women who are breastfeeding will be excluded
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History of cervical cancer or anal cancer
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History of active malignancy, including basal/squamous cell skin cancer
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Concurrent illness, such as known psychiatric disorders or substance abuse (i.e., average alcohol consumption of more than 3 drinks per day), which in the opinion of the investigators would compromise either the patient or the integrity of the data
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Patients on anticoagulation or with bleeding disorders should be evaluated by a physician for risk/benefit of bleeding disorders with intramuscular injections prior to study enrollment; patients determined to be at high risk for bleeding with intramuscular injections will be excluded
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham Cancer Center | Birmingham | Alabama | United States | 35233 |
| 2 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 3 | UCSF Medical Center-Mount Zion | San Francisco | California | United States | 94115 |
| 4 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 5 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
| 6 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Marc T Goodman, Northwestern University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2017-00116
- NCI-2017-00116
- N01-CN-2012-00035
- NCI2015-06-02
- NWU2015-06-02
- N01CN00035
- P30CA060553