Clinical trial NCT00667563: Vaccine Therapy in Preventing HPV in HIV-Positive Women in India
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Cancer
Nonneoplastic Condition
Precancerous Condition
Keywords: human papilloma virus infection
cervical cancer
cervical intraepithelial neoplasia
HIV infection
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
First posted: 2008-04-28
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0
timeFrame: 52 weeks from study entry
measure: Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count
timeFrame: Screening/Week 0, Weeks 2, 10, 26, and 52.
measure: Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28
timeFrame: Week 28
measure: Number of Patients With a Significant Increase in HIV Viral Load
timeFrame: Screening/week 0, weeks, 2, 10, 26 and 52
measure: Number of Patients With Detectable Antibodies to HPV-6
timeFrame: 28 weeks
measure: Number of Patients With Detectable Antibodies to HPV-11
timeFrame: 28 weeks
measure: Number of Patients With Detectable Antibodies to HPV-18
timeFrame: 28 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chennai
country: India
facility: YRG Care
Study officials:
affiliation: University of California, San Francisco
name: Joel Palefsky, MD
role: STUDY_CHAIR
affiliation: YRG Care
name: N. Kumarasamy, MD
role: PRINCIPAL_INVESTIGATOR
References: