No registrations found.
ID
Source
Brief title
Health condition
DNA tattoo vaccination; uVIN; usual vulvar intraepithelial neoplasia; HPV16; sig-HELP-E6SH/E7SH-kdel; vulvaire intraepitheliale neoplasie; HPV vaccinatie
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objectives:
• To study the systemic HPV-specific immune response of two naked DNA vaccines
encoding sig-HELP-kdel and shuffled HPV16 E6 or E7 gene products (sig-HELPE6SH/
E7SH-kdel).
Secondary outcome
Secondary objective:
• To study the safety of sig-HELP-E6SH/E7SH-kdel.
• To study the clinical response to vaccination of sig-HELP-E6SH/E7SH-kdel.
Exploratory objectives:
• To study the migratory capacity of HPV16-specific T cells by analysis of their
presence in vaccine sites.
• The effect of vaccination on the immune infiltrate in VIN lesion microenvironment will
be determined by multicolour fluorescent immunohistochemistry.
Background summary
This is a phase I/II trial to evaluate the toxicity, immunogenicity and clinical response of two novel HPV DNA vaccines (sig-HELP-E6SH-kdel and sig-HELPE7SH-kdel), applied by DNA tattoo vaccination, in uVIN patients. This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies. The first cohort of patients (n=5) will be vaccinated with 2 mg of sig-HELP-E6SH/E7SH-kdel on days 0, 14, 28 and 42. Just before administration, 1 mg of sig-HELP-E6SH-kdel will be mixed with 1 mg of sig-HELP-E7SH-kdel to have 2 mg of the combined E6SH/E7SH. After all 5 patients received all vaccination, we will perform an interim analysis by flow cytometry. There are 2 possible scenarios after the interim analysis:
1. Acceptable immune response
2. Non acceptable immune response
Depending on the outcome of the interim analysis we will continue with the second cohort of patients.
1. Additional cohort of 9 patients
2. Termination of the trial
Study objective
This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies.
Study design
Day -30 to 1: screening. Day 0: vaccination, PBMCs. Day 14: vaccination. Day 28: vaccination, PBMCs. Day 42: vaccination. Day 56: follow-uw, PBMC. Day 84: follow-up, PBMC. Month 3: follow-up, biopsy uVIN. Month 6: follow-up. Month 9: follow-up. Month 12: follow-up.
Intervention
This is a phase I/II trial to evaluate the toxicity, immunogenicity and clinical response of two novel HPV DNA vaccines (sig-HELP-E6SH-kdel and sig-HELPE7SH-kdel), applied by DNA tattoo vaccination, in uVIN patients. This study will allow us to define the optimal dosis and value of these HPV DNA vaccines for the treatment of HPV16+ (pre)malignancies. The first cohort of patients (n=5) will be vaccinated with 2 mg of sig-HELP-E6SH/E7SH-kdel on days 0, 14, 28 and 42. Just before administration, 1 mg of sig-HELP-E6SH-kdel will be mixed with 1 mg of sig-HELP-E7SH-kdel to have 2 mg of the combined E6SH/E7SH. After all 5 patients received all vaccination, we will perform an interim analysis by flow cytometry. There are 2 possible scenarios after the interim analysis:
1. Acceptable immune response
2. Non acceptable immune response
Depending on the outcome of the interim analysis we will continue with the second cohort of patients.
1. Additional cohort of 9 patients
2. Termination of the trial
Jossie Rotman
Obstetrics & Gynecology/Immunotherapy Lab
Amsterdam
The Netherlands
(020-44)42175 Mob: +31622706702
Mail: j.rotman@vumc.nl
Jossie Rotman
Obstetrics & Gynecology/Immunotherapy Lab
Amsterdam
The Netherlands
(020-44)42175 Mob: +31622706702
Mail: j.rotman@vumc.nl
Inclusion criteria
• Age above 18 years
• Willing and able to undergo the planned study procedures
• Written informed consent
• Histologically proven visible uVIN lesion (histology ≤3 months prior to enrolment and at
least 6 weeks after last treatment)
• HPV16-positive VIN lesion (to be determined on archival tumour tissue (≤10 years old); if
not available a new biopsy will be required)
• No indication of an active infectious disease: HIV, HCV and HBV negative
• No history of autoimmune disease or systematic undercurrent disease which might affect
immunocompetence
• Adequate bone marrow (WBC > 3.0/nL, platelets > 100/nL), renal function (creatinine
clearance > 40 mL/min), and liver function (bilirubin < 1.5 x ULN, normal blood
coagulation)
Exclusion criteria
• Prior treatment with anti-HPV agents
• Participation in a study with another investigational drug within 30 days prior to enrolment
in this study
• Severe cardiac, respiratory, or metabolic disease
• Use of systemic steroids or other immunosuppressive drugs
• Use of oral anticoagulant drugs (except ascal)
• Severe infections requiring antibiotics
• Any treatment for the uVIN lesion within 6 weeks prior to the enrolment (including
imiquimod)
• Lactation or pregnancy (if applicable)
• Not willing to take adequate contraceptive measures (if applicable)
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 |
|---|---|
| NTR-new | NL7139 |
| NTR-old | NTR7337 |
| Other | HPV16 E6-E7 : N16SIG |