Clinical trial NCT01209325: Vaccine Therapy in Preventing Human Papillomavirus Infection in Young HIV-Positive Male Patients Who Have Sex With Males
Official title: AMC-072: Protective Effect of Quadrivalent Vaccine in Young HIV-Positive Males Who Have Sex With Males
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anal Cancer
Nonneoplastic Condition
Penile Cancer
Precancerous Condition
Keywords: human papilloma virus infection
anal cancer
penile cancer
HIV infection
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
name: University of Arkansas
name: Merck Sharp & Dohme LLC
name: AIDS and Cancer Specimen Resource
First posted: 2010-09-27
Enrollment: 149
Sex: MALE
Minimum age (years): 13
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to prevent viral infection.

PURPOSE: This phase II trial is studying how well vaccine therapy works in preventing human papillomavirus (HPV) infection in young HIV-positive male patients who have sex with males.

Detailed description: OBJECTIVES:

Primary

* To determine the protective effect of the HPV-6, -11, -16, -18 vaccine in preventing penile/scrotal condyloma and HPV-6, -11, -16, -18- associated perianal/anal disease in HIV-positive males who have sex with males (MSM) age 13-26 years by comparing the incidence of these lesions among those naïve to the relevant HPV type(s) at baseline to those who are not naïve at baseline.
* To determine the protective effect of the HPV-6, -11, -16, -18 vaccine in preventing persistent anogenital infection with HPV-6, -11, -16, or 18 in HIV-positive MSM age 13-26 years by comparing the incidence of persistent infection among those naïve to the relevant HPV type(s) at baseline to those who are not naïve at baseline.
* To determine the protective effect of the HPV-6, -11, -16, -18 vaccine in preventing anogenital lesions associated with HPV 6,-11,-16, -18 and persistent infection with these types, in HIV-positive MSM age 13-26 years by comparing the incidence of lesions and persistent infection among those naïve to the relevant types at baseline to incident lesions and infection among MSM naïve to these HPV types who participated in the Merck 020 protocol and who received placebo as part of the protocol.

Secondary

* To define the safety of the HPV-6, -11, -16, -18 vaccine in HIV-positive MSM age 13-26 years.
* To evaluate the levels and persistence of HPV 6, 11, 16 and 18 Ab titers after the vaccination series among subjects who are seropositive and seronegative at baseline.
* To examine whether the protective effect and antibody titers vary as a function of the following at the time of initial vaccination: subject age, HAART treatment status, HIV viral load, CD4 + T-cell count, and nadir CD4 level.

Tertiary

* To quantify anogenital HPV DNA viral load prior to and after receipt of the quadrivalent HPV vaccine.
* To identify and quantify HPV types in the oral cavity of HIV-positive MSM prior to and after receipt of the quadrivalent HPV vaccine.
* To identify HPV strain variants among HIV-positive participants prior to and after receipt of the quadrivalent HPV vaccine.
* Assess the prevalence and incidence of urinary and gonorrhea and Chlamydia trachomatis infection at baseline and their relationship with prevalent and incident anogenital HPV infection and anal condyloma or AIN.
* To characterize young men's risk perceptions, sexual behaviors, and STI diagnosis after HPV vaccination.

OUTLINE: This is a multicenter study.

Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine intramuscularly on day 1 and in weeks 8 and 24.

Blood and tissue samples may be collected periodically for laboratory studies.

After completion of study treatment, patients are followed up for 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Men with a history of at least one male sexual partner

  * "Men" is defined as those documented "male" at birth (including male-to-female transgendered persons)
* HIV-1 infection as documented by any federally approved, licensed HIV test performed in conjunction with screening (ELISA, western blot, or other approved test)

  * Alternatively, this documentation may include a record that another physician has documented that the patient has HIV based on prior ELISA and western blot, or other approved diagnostic tests
* Meets one of the following sets of criteria:

  * Patients receiving antiretroviral therapy:

    * Receipt of antiretroviral therapy for at least 3 months prior to entry
    * No change in antiretroviral therapy within 30 days prior to entry
  * Patients not receiving antiretroviral therapy:

    * CD4-cell count ≥ 350 cells/mm³ within 90 days prior to study entry
    * No plans to start antiretroviral therapy prior to Week 28
* Normal anal cytological result, LSIL/condyloma, or ASCUS result within 90 days prior to entry, and no HGAIN on biopsy

  * No current or history of anal or peri-anal carcinoma
  * No anal cytological result of HSIL, atypical squamous cells suggestive of HSIL (ASC-H), or suggestive of invasive carcinoma at screening; or history of these results
* No presence of penile or scrotal condyloma, LGAIN (condyloma or AIN 1), HGAIN (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3), or invasive carcinoma at pre-entry on biopsy
* No history of HGAIN

PATIENT CHARACTERISTICS:

* Karnofsky performance score ≥ 70 within 45 days prior to entry
* Absolute neutrophil count (ANC) \> 750 cells/mm\^3
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/mm\^3
* AST (SGOT), ALT (SGPT) ≤ 3 times upper limit of normal (ULN)
* Total or conjugated (direct) bilirubin ≤ 2.5 times ULN within 45 days before study entry, with the exception of isolated hyperbilirubinemia that is considered due to atazanavir
* Calculated creatinine clearance ≥ 60 mL/min
* No hemophilia
* No active drug or alcohol use or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements
* No serious illness requiring systemic treatment and/or hospitalization within 45 days prior to entry
* No serious medical or psychiatric illness that, in the opinion of the site Investigator, will interfere with the ability of the subject to give informed consent or adhere to the protocol
* No allergy to yeast or any of the components of Gardasil

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior splenectomy
* No prior receipt of Gardasil or other HPV vaccine
* No use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids for greater than 14 days, investigational vaccines, interleukins, interferons, growth factors, or IVIG within 45 days prior to study entry
* No expected use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids used for greater than 14 days, investigational vaccines, interleukins, interferons, growth factors, or IVIG during study followup

  * No patients with hepatitis C who expect to initiate treatment for hepatitis C (e.g., interferons) during this trial
* Not currently receiving anticoagulation therapy other than acetylsalicylic acid

Primary outcomes:
measure: Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 6 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 11 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 16 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 18 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of Persistent Anogenital Infection With HPV 6 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of Persistent Anogenital Infection With HPV 11 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of Persistent Anogenital Infection With HPV 16 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of Persistent Anogenital Infection With HPV 18 DNA
timeFrame: Post Month 7 through Month 24
measure: Incidence of HGAIN Associated With HPV 6
timeFrame: Post month 7 through month 24
measure: Incidence of HGAIN Associated With HPV 11
timeFrame: Post month 7 through month 24
measure: Incidence of HGAIN Associated With HPV 16
timeFrame: Post month 7 through month 24
measure: Incidence of HGAIN Associated With HPV 18
timeFrame: Post month 7 through month 24
measure: Incidence of Penile/Scrotal Condyloma in HPV 6 Naive and Prior Exposed Participants
timeFrame: Post month 7 through month 24
measure: Incidence of Penile/Scrotal Condyloma in HPV 11 Naive and Prior Exposed Participants
timeFrame: Post month 7 through month 24
measure: Incidence of Penile/Scrotal Condyloma in HPV 16 Naive and Prior Exposed Participants
timeFrame: Post month 7 through month 24
measure: Incidence of Penile/Scrotal Condyloma in HPV 18 Naive and Prior Exposed Participants
timeFrame: Post month 7 through month 24
Secondary outcomes:
measure: Occurrence of Grade ≥ 3 Adverse Events (AEs) That Were Possibly, Probably, or Definitely Related to the Vaccine
timeFrame: Through Month 24
measure: Geometric Mean Titers for HPV 6
timeFrame: Baseline through month 24
measure: Geometric Mean Titers for HPV 11
timeFrame: Baseline through month 24
measure: Geometric Mean Titers for HPV 16
timeFrame: Baseline through 24 months
measure: Geometric Mean Titers for HPV 18
timeFrame: Baseline through 24 months
measure: Geometric Mean Titers for HPV 6 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level
timeFrame: at 7 and 24 Months
measure: Geometric Mean Titers for HPV 11 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level
timeFrame: at 7 and 24 Months
measure: Geometric Mean Titers for HPV 16 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level
timeFrame: at 7 and 24 Months
measure: Geometric Mean Titers for HPV 18 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level
timeFrame: at 7 and 24 Months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical AIDS Research and Education (CARE) Center
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: Ruth M. Rothstein Core Center at Cook County Hospital
state: Illinois
city: Boston
country: United States
facility: Fenway Community Health
state: Massachusetts
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Laser Surgery Care
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Memphis
country: United States
facility: St. Jude's Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Thomas Street Health Center
state: Texas
city: Houston
country: United States
facility: Dan L. Duncan Cancer Center at Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Comprehensive Cancer Center
Study officials:
affiliation: University of California, San Francisco
name: Joel Palefsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kahn JA, Belzer M, Chi X, Lee J, Gaur AH, Mayer K, Martinez J, Futterman DC, Stier EA, Paul ME, Chiao EY, Reirden D, Goldstone SE, Ortiz Martinez AP, Cachay ER, Barroso LF, Da Costa M, Wilson CM, Palefsky JM; AIDS Malignancy Consortium and Adolescent Medicine Trials Network for HIV/AIDS Interventions. Pre-vaccination prevalence of anogenital and oral human papillomavirus in young HIV-infected men who have sex with men. Papillomavirus Res. 2019 Jun;7:52-61. doi: 10.1016/j.pvr.2019.01.002. Epub 2019 Jan 15.