Preventive Human Papilomavirus (HPV) Vaccine Trial in Kidney Transplant Recipients

PRIMARY OBJECTIVES:

I. 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:

I. To evaluate the following in female kidney transplant recipients who receive >= 1 doses of
the Gardasil 9 HPV vaccine prior to transplantation: HPV vaccine-type-specific seroconversion
rates at 12-months post-transplantation stratified by: a) number of doses (1, 2, or 3) of the
vaccine given pre-transplant; b) time elapsed between last vaccine dose and the transplant
procedure; c) variations in dosing and types of post-transplant immunosuppressant
medications; and interactions with type of transplant surgery (living donor/deceased donor),
and d) differences in human leukocyte antigen (HLA) histocompatibility between donor and
recipient.

II. To evaluate the following in female kidney transplant recipients who receive >= 1 doses
of the Gardasil 9 HPV vaccine >= 30 days prior to transplantation: 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.

III. To evaluate the following in female kidney transplant recipients who receive >= 1 doses
of the Gardasil 9 HPV vaccine >= 30 days prior to transplantation: 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.

IV. To evaluate the following in female kidney transplant recipients who receive >= 1 doses
of the Gardasil 9 HPV vaccine >= 30 days prior to transplantation: 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.

OUTLINE:

Patients 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.

Inclusion Criteria:

- Female candidate for renal transplant, expected to undergo transplant surgery >= 30
days and =< 12 months after enrollment

- 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

- 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

- Note: 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 to also open enrollment to recipients of deceased donor kidneys

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

- 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

- Ability to understand and the willingness to sign a written informed consent document
and medical release form

- Willing and able to comply with trial protocol and follow-up

Exclusion Criteria:

- Previous prophylactic HPV vaccination

- Prior organ transplant

- Anticipated desensitization treatment; this decision to exclude 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,
women 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 in the study

- Current use of any other investigational agents

- History of allergic reactions to yeast or attributed to compounds of similar chemical
or biologic composition to Gardasil 9 HPV vaccine

- 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

- 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

- History of cervical cancer or anal cancer

- History of active malignancy, including basal/squamous cell skin cancer

- Prior hysterectomy

- 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

- 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