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

This study has been completed.
Sponsor:
Collaborators:
The EMMES Corporation
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00667563
First received: April 25, 2008
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Nonneoplastic Condition
Precancerous Condition
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • 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


Enrollment: 150
Study Start Date: August 2009
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667563

Locations
India
YRG Care
Chennai, India, 600113
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
The EMMES Corporation
Investigators
Study Chair: Joel Palefsky, MD University of California, San Francisco
Principal Investigator: N. Kumarasamy, MD YRG Care
  More Information

Additional Information:
No publications provided

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT00667563     History of Changes
Other Study ID Numbers: AMC-054, U01CA121947, CDR0000593634
Study First Received: April 25, 2008
Results First Received: January 23, 2014
Last Updated: August 27, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board
India: Drugs Controller General of India
India: Indian Council of Medical Research
India: Institutional Review Board

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
human papilloma virus infection
cervical cancer
cervical intraepithelial neoplasia
HIV infection

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
HIV Seropositivity
Precancerous Conditions
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on September 11, 2014