Vaccine Therapy in Preventing HPV in HIV-Positive Women in India - Full Text View

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:	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:

MedlinePlus related topics: Cancer Cervical Cancer HIV/AIDS

Drug Information available for: Human Papillomaviruses

Genetic and Rare Diseases Information Center resources: Cervical Intraepithelial Neoplasia

U.S. FDA Resources

Further study details as provided by AIDS Malignancy 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.

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 to 120 Years (Adult, Senior)
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 Consortium

National Cancer Institute (NCI)

The EMMES Corporation

Investigators


Study Chair:	Joel Palefsky, MD	University of California, San Francisco
Principal Investigator:	N. Kumarasamy, MD	YRG Care

More Information


Responsible Party:	AIDS Malignancy 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:	February 1, 2016
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 Consortium:


human papilloma virus infection cervical cancer cervical intraepithelial neoplasia HIV infection

Additional relevant MeSH terms:


Disease Uterine Cervical Neoplasms HIV Seropositivity Precancerous Conditions Pathologic Processes 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 Vaccines Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016