Evaluation of the capacity of a HPV 16 peptide vaccine to install a long term HPV-specific T cell response, to define the importance of a booster vaccine after 1 year, the induction of Cytotoxic T lymphocyte (CTL) immunity against HPV16E6 and E7 and…
ID
Source
Brief title
Condition
- Cervix disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
By comparing blood drawn at different time points during the study, in vitro
analysis will reveal the induction of Cytotoxic T lymphocyte (CTL) immunity
against HPV16E6 and E7, induction of HPV16-specific T-helper (Th) type 1 cells
to evaluate the capacity of this vaccination strategy to install long term
HPV-specific T cell immunity.
Secondary outcome
By comparing the results between the patients receiving a placebo after 1 year
and patients boosted with the HPV16 peptides, the capacity of re-vaccination to
boost the HPV16-specific response will be evatluated.
Furthermore in vivo analysis via Skin tests will also be used to measure the
presence and type of immunity against HPV16 E2, E6- and E7 peptides.
Background summary
Vaccination with HPV 16 long peptides is known to give a strong systemic
HPV16-specific type 1 T-cell response in patients with cervical cancer and VIN.
An important factor for a vaccine to be effective is the capacity to create a
long term HPV-specific T cell response to provide a long term protective anti
tumor effect. The capacity of an HPV 16 long peptide vaccination strategy to
install such a long term immune response and the importance of re-vaccination
after one year to boost this response is unknown.
Study objective
Evaluation of the capacity of a HPV 16 peptide vaccine to install a long term
HPV-specific T cell response, to define the importance of a booster vaccine
after 1 year, the induction of Cytotoxic T lymphocyte (CTL) immunity against
HPV16E6 and E7 and the induction of HPV16-specific T-helper (Th) type 1 cells.
Study design
This is a placebo-controlled randomised clinical study.
Intervention
40 Patients will receive two sequential vaccinations containing a dose of 50ug
per peptide with a 3-week interval (week 0, 3). After 1 year patients will be
randomized to receive a booster vaccine with peptide (n=20) or placebo (n=20).
10 Patients will receive a matching placebo at all three vaccination time
points.
Study burden and risks
Blood samples required for in vitro analysis of HPV-specific T cell responses,
will be taken at five time points: before the first vaccination (week 0), 4
weeks after the first series of two vaccinations (week 7), before the booster
vaccination (week 52), 4 weeks after the booster vaccination (week 56) and 12
months after the booster vaccination (week 104). Skin DTH tests and HPV typing
will be performed three times (before the first vaccination, before the boost
vaccination and at 2 years). In 2 years 11 visits to the LUMC clinics are
needed. The risks for, and burden to patients will be minimal considering
previous experiences with the same vaccination. The skin testing and
vaccinating will be performed under close medical supervision at the
gynaecology department*s day care unit at the LUMC.
Postbus 9600,
2300 RC Leiden
NL
Postbus 9600,
2300 RC Leiden
NL
Listed location countries
Age
Inclusion criteria
- patiënts of 18 years and older
- willing and able to comply with the protocol, and provide informed consent in accordance with institutional and regulatory guidelines
- histological evidence of CIN, grade I or cytological evidence of a persistent PAP II (two consecutive pap II smears with a 6 month interval)
- performance status 1 or 2 at the WHO scale, or 60 on the Karnofsky scale
- baseline laboratory findings; white blood cells (WBC) > 3,000 x 10 9/l, lymphocytes >1,000 x 10 9/l, platelets > 100 x 10 9/l, and hematocrit > 30%, HIV- and HBV-negative
- patients of child-bearing potential should test negative using a pregnancy test and agree to utilize effective contraception or remain abstinent during the entire treatment period of the study
Exclusion criteria
- indication of a current active infectious disease other than HPV16,
- history of an autoimmune disease or other systemic intercurrent disease that might affect patient*s immunocompetence
- history of a second malignancy except curatively treated low-stage tumours with a histology that can be differentiated from the vulvar/cervical cancer type
- radiotherapy, chemotherapy or other potentially immunosuppressive therapy administered within 4 weeks prior to the colposcopy visit
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-004548-22-NL |
| CCMO | NL14057.000.06 |