This study aims to reveal whether vaccination of women with HPV 16+ cervical intraepithelial neoplasia not only results in a strong systemic T-cell response, but also endows these T-cells with the capacity to infiltrate HPV16-induced lesions.…
ID
Source
Brief title
Condition
- Cervix disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Before first vaccination and 4 weeks after second vaccination (week 7),
histological material will be tested for the quantity of different infiltrating
immune cells.
Secondary outcome
Characterisation of the HPV16-specific infiltrating T-cells; cytokine milieu
and presence of HPV16.
Background summary
Patients with (pre-) malignant cervical lesions often have a weak or absent
spontaneous HPV-specific T-cell response thought to be important in the
clearance of infection and disease. Vaccination with HPV 16 E6 and E7 long
peptides is known to give a strong systemic HPV16-specific type 1 T-cell
response and seems excellently suited to overcome these deficits. For the
rational design of potentially successful vaccine candidates it is important to
determine if vaccine-regimens succeed in driving the migration of HPV16+
T-cells into the HPV16+ lesions and to establish whether the presence of such
immune cells is related to clearance of HPV16.
Study objective
This study aims to reveal whether vaccination of women with HPV 16+ cervical
intraepithelial neoplasia not only results in a strong systemic T-cell
response, but also endows these T-cells with the capacity to infiltrate
HPV16-induced lesions. Furthermore it will evaluate the systemic HPV16 E6 and
E7 specific T cell immune response and the clearance of the HPV infection in
response to vaccination.
Study design
This is a placebo-controlled randomised clinical study.
Intervention
Half of the patients will be vaccinated twice with a mix of HPV E6 and E7 long
peptides at a dose of 300µg/peptide, the other half will be vaccinated with a
matching placebo.
Study burden and risks
From each study patient, at baseline, cervical swaps and small biopsies will be
taken as part of the routine diagnosis of CIN. 4 weeks after second vaccination
histological material will be obtained by surgical excision of the cervical
lesion. 2-4 weeks after surgery, patients will undergo a skin test. At three
occasions during the study 70 mL of peripheral blood will be obtained via
venapuncture. At least 4 visits to the LUMC clinics are needed. As compared to
the routine treatment of CIN patients, only the vaccinations, the blood draws
and the skin testing are extra procedures for this study. 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
- patients 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 II or III, HPV16 positive
- 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 | EUCTR2006-004443-30-NL |
| CCMO | NL14015.000.06 |