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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00667563
First received: April 25, 2008
Last updated: March 7, 2014
Last verified: March 2014

April 25, 2008
March 7, 2014
August 2009
November 2012   (final data collection date for primary outcome measure)
  • Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0 [ Time Frame: 52 weeks from study entry ] [ Designated as safety issue: Yes ]
    Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients
  • Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count [ Time Frame: Screening/Week 0, Weeks 2, 10, 26, and 52. ] [ Designated as safety issue: No ]
    Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests
  • Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline
  • Number of Patients With a Significant Increase in HIV Viral Load [ Time Frame: Screening/week 0, weeks, 2, 10, 26 and 52 ] [ Designated as safety issue: Yes ]
    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
  • Number of Patients With Detectable Antibodies to HPV-6 [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
    Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline
  • Number of Patients With Detectable Antibodies to HPV-11 [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
    Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline
  • Number of Patients With Detectable Antibodies to HPV-18 [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
    Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline
  • Safety, in terms of grade 3 or 4 adverse events attributed to the vaccine, according to NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Significant decrease (at the 0.05 significance level) in CD4+ cell count or HIV RNA rise from baseline of ≥ 1.0 log10 in the level of quantification (or > 200 copies/mL in patients < 50 years old at study entry) [ Designated as safety issue: No ]
  • Detectable HPV antibody to HPV 16, 18, 6 or 11 at 1 month after the completion of HPV vaccination series (week 28) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00667563 on ClinicalTrials.gov Archive Site
Not Provided
HPV antibody titers to types 6, 11, 16, and 18 at baseline and at weeks 8, 24, and 52 [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vaccine Therapy in Preventing HPV in HIV-Positive Women in India
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

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Cervical Cancer
  • Nonneoplastic Condition
  • Precancerous Condition
  • 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.
    Other Name: HIV viral load test and HPV neutralization assays.
  • Genetic: 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.
Experimental: Gardasil Vaccination
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Interventions:
  • Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
  • Genetic: DNA analysis
  • Genetic: polymerase chain reaction
  • Other: cytology specimen collection procedure
  • Procedure: colposcopic biopsy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
150
November 2012
November 2012   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
India
 
NCT00667563
CDR0000593634, U01CA121947, AMC-054
No
AIDS Malignancy Clinical Trials Consortium
AIDS Malignancy Clinical Trials Consortium
National Cancer Institute (NCI)
Study Chair: Joel Palefsky, MD University of California, San Francisco
Principal Investigator: N. Kumarasamy, MD YRG Care
AIDS Malignancy Clinical Trials Consortium
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP