Clinical trial NCT00513526: Human Papillomavirus Vaccine Therapy in Treating Men With HIV-1 Infection
Official title: A Single-Arm, Open-Label Pilot Trial of the Safety and Immunogenicity of a Quadrivalent Human Papillomavirus Vaccine in HIV-1-Infected Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infection
Precancerous Condition
Keywords: infection
low-grade squamous intraepithelial lesion
atypical squamous cells of undetermined significance
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
First posted: 2007-08-08
Enrollment: 112
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from human papillomavirus may help the body build an effective immune response to kill HIV cells.

PURPOSE: This phase II trial is studying the side effects and how well human papillomavirus vaccine therapy works in treating men with HIV-1 infection.

Detailed description: OBJECTIVES:

Primary

* To assess the safety and tolerability of quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine in HIV-infected men.
* To assess the immunogenicity of the quadrivalent HPV vaccine for types 6, 11, 16 and 18 in subjects who are antibody-negative at baseline.

Secondary

* To evaluate the changes in plasma HIV-1 RNA and CD4+ count after the vaccination series.
* To describe the associations of CD4+ count, nadir CD4+ count, and age on antibody response.
* To evaluate the levels and persistence of HPV 6, 11, 16, and 18 antibody titers after the vaccination series among subjects according to serostatus at baseline.
* To evaluate the oral levels of serum IgA before and after the vaccination series.

Tertiary

* To evaluate prevalent and incident HPV infections in the anal canal.
* To evaluate cytological and histological abnormalities in the anal canal.
* To evaluate prevalent and incident HPV infections in the oral cavity.
* To compare oral and anal compartmental shedding of HPV before and after vaccination.

OUTLINE: This is a multicenter study.

Patients receive quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and weeks 8 and 24.

After completion of protocol therapy, patients are followed at 7, 12, and 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot prior to 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
* Anal human papilloma virus DNA PCR-negative for either type 16 and/or type 18 within 90 days prior to entry
* If receiving antiretroviral therapy:

  * Receipt of antiretroviral therapy for at least 6 months prior to entry
  * No change in antiretroviral therapy within 30 days prior to entry
  * CD4 cell count \> 200 cells/mm³ within 90 days prior to study entry
  * HIV-1 RNA \< 200 copies/mL within 90 days prior to entry
* If 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, or atypical squamous cell of undetermined significance or low-grade squamous intraepithelial lesions (SIL) result within 90 days prior to entry

Exclusion criteria:

* Current or history of anal or perianal carcinoma
* Anal cytological result of high-grade SIL (HSIL), atypical squamous cells suggestive of HSIL, or suggestive of invasive carcinoma at screening or a history of these results
* Presence of high-grade anal intraepithelial neoplasm (HGAIN) (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3), or invasive carcinoma at pre-entry, or history of HGAIN

  * Current or history of anal or peri-anal condyloma is allowed

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Karnofsky performance status 70-100%
* Absolute neutrophil count \> 750 cells/mm³
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/mm³
* Creatinine clearance ≥ 60 mL/min
* AST and ALT ≤ 3 times ULN
* Total or conjugated (direct) bilirubin ≤ 2.5 times ULN

Exclusion criteria:

* Serious medical or psychiatric illness, active drug or alcohol use, or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements
* Serious illness requiring systemic treatment and/or hospitalization within the past 45 days
* Allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
* Hemophilia

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

* See Disease Characteristics

Exclusion criteria:

* Prior splenectomy
* Currently receiving anticoagulation therapy other than acetylsalicylic acid
* Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or IVIG within 45 days prior to study entry

  * Routine standard of care, including hepatitis A or B, influenza, or pneumococcal and tetanus vaccines are not excluded
  * Hepatitis C co-infected patients are eligible provided no concurrent initiation of treatment for hepatitis C
* Prior receipt of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine or other HPV vaccine

Primary outcomes:
measure: Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine
timeFrame: All study visits
measure: Detectable Human Papillomavirus (HPV) Antibody to Type 6 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 6 at Baseline
timeFrame: Week 28
measure: Detectable Human Papillomavirus (HPV) Antibody to Type 11 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 11 at Baseline
timeFrame: Week 28
measure: Detectable Human Papillomavirus (HPV) Antibody to Type 16 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 16 at Baseline
timeFrame: Week 28
measure: Detectable Human Papillomavirus (HPV) Antibody to Type 18 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 18 at Baseline
timeFrame: Week 28
Secondary outcomes:
measure: Longitudinal Changes in CD4+ Cell Count From Baseline
timeFrame: Week 0, 4, 12, 28
measure: Longitudinal Changes in Plasma HIV-1 RNA From Baseline
timeFrame: Week 0, 4, 12, 28
measure: HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
timeFrame: weeks 0, 28, and 76
measure: HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
timeFrame: weeks 0, 28, and 76
measure: HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
timeFrame: weeks 0, 28, and 76
measure: HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
timeFrame: weeks 0, 28, and 76
measure: Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series
timeFrame: Weeks 0, 28 and 76
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Clinical AIDS Research and Education (CARE) Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
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: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Weill Medical College of Cornell University
name: Timothy J. Wilkin, MD, MPH
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Joel Palefsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kang M, Umbleja T, Ellsworth G, Aberg J, Wilkin T. Effects of Sex, Existing Antibodies, and HIV-1-Related and Other Baseline Factors on Antibody Responses to Quadrivalent HPV Vaccine in Persons With HIV. J Acquir Immune Defic Syndr. 2022 Apr 1;89(4):414-422. doi: 10.1097/QAI.0000000000002891.
citation: Wilkin T, Lee JY, Lensing SY, Stier EA, Goldstone SE, Berry JM, Jay N, Aboulafia D, Cohn DL, Einstein MH, Saah A, Mitsuyasu RT, Palefsky JM. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis. 2010 Oct 15;202(8):1246-53. doi: 10.1086/656320.