Vaccine Therapy in Preventing HPV in HIV-Positive Women in India

Cervical Cancer Clinical Trial

Official title:

A Single-Arm, Open-Label Pilot Study of the Safety and Immunogenicity of the Merck Quadrivalent Human Papillomavirus Vaccine Among HIV-Positive Women in India

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00667563
• Other study ID #: AMC-054
• Secondary ID: U01CA121947CDR00
• Status: Completed
• Phase: Phase 1
• Start date: August 2009
• Est. completion date: November 2012

Study information

• Verified date: February 2024
• Source: AIDS Malignancy Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Vaccines made from virus proteins may help the body build an effective immune response to prevent cervical cancer. PURPOSE: This pilot study is looking at the side effects of a human papillomavirus vaccine and how well it works in preventing cervical cancer in women in India with HIV-1 infection.

Description:

OBJECTIVES: Primary - Assess the safety of the Gardasil® quadrivalent human papillomavirus (HPV) (types 6, 11, 16,18) virus-like-particle vaccine with vs without prior exposure to one or more of the HPV types in the vaccine in HIV-positive women in Chennai, India. - Determine the effect of the vaccine on HIV viral load and CD4+/CD8+ levels in these patients. - Determine the proportion of these patients who respond serologically to the HPV vaccine and the kinetics of their response. Secondary - Determine the prevalence and incidence of cervical intraepithelial neoplasia in these patients. - Determine the spectrum of cervical HPV types in these patients at baseline, 9 months, and 1 year after vaccination. OUTLINE: This is a multicenter study. Patients receive quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and once in weeks 8 and 24. Patients undergo cervical cell, buccal cell, and blood sample collection at baseline and periodically after vaccination for immunologic and virologic studies. Cervical cytology specimens are examined by polymerase chain reaction to detect HPV 6, 11, 16, or 18 DNA, as well as 35 other HPV types. Blood samples are analyzed for CD4+/CD8+ cell count, plasma HIV-1 RNA levels, and serum HPV antibody titers for HPV types 6, 11, 16, and 18. Some plasma samples will be stored for future HPV pseudovirion neutralization assays. After completion of study therapy, patients are followed periodically for up to 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot before study entry
• HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test
• Meets 1 of the following criteria:
• Nadir CD4 level of = 350 cells/mm³ and receiving highly active antiretroviral therapy (HAART) for at least 6 months before study entry
• Nadir CD4 level of > 350 cells/mm³ and not receiving HAART at the time of study entry
• No known history of high-grade CIN or cervical cancer

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• ANC > 750 cells/mm³
• Hemoglobin = 9.0 g/dL
• Platelet count = 100,000/mm³
• Serum creatinine = 3 times upper limit of normal (ULN)
• AST and ALT = 3.0 times ULN
• Conjugated (direct) bilirubin = 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active drug or alcohol use or dependence that would interfere with adherence to study requirements, in the opinion of the site Investigator
• No serious illness requiring systemic treatment and/or hospitalization within the past 45 days
• No allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 45 days since prior systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin
• Routine standard of care, including hepatitis B, influenza, and tetanus vaccines are allowed

Related Conditions & MeSH terms

• Cervical Cancer
• Disease
• Nonneoplastic Condition
• Precancerous Condition
• Precancerous Conditions
• Uterine Cervical Neoplasms

Intervention

Biological:
• quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.

Genetic:
• DNA analysis
Weeks 0, 2, 10, 26, and 52.
• polymerase chain reaction
Screening, week 36, and week 52.

Other:
• cytology specimen collection procedure
Screening, week 36, and week 52.

Procedure:
• colposcopic biopsy
Screening, week 36, and week 52.

Locations

Country	Name	City	State
India	YRG Care	Chennai

Sponsors (3)

Lead Sponsor	Collaborator
AIDS Malignancy Consortium	National Cancer Institute (NCI), The Emmes Company, LLC

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0	Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients	52 weeks from study entry
Primary	Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count	Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests	Screening/Week 0, Weeks 2, 10, 26, and 52.
Primary	Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28	Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline	Week 28
Primary	Number of Patients With a Significant Increase in HIV Viral Load	Number of patients with a significant increase in HIV viral load defined as > 1 log increase in HIV load from baseline on 2 consecutive occasions	Screening/week 0, weeks, 2, 10, 26 and 52
Primary	Number of Patients With Detectable Antibodies to HPV-6	Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline	28 weeks
Primary	Number of Patients With Detectable Antibodies to HPV-11	Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline	28 weeks
Primary	Number of Patients With Detectable Antibodies to HPV-18	Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline	28 weeks

External Links

•   Clinical trial summary for AMC-054