Human Papillomavirus Vaccine Therapy in Treating Men With HIV-1 Infection

• Sponsor: AIDS Malignancy Consortium (Other)
• Overall Status: Completed
• CT.gov ID: NCT00513526
• Collaborator: National Cancer Institute (NCI) (NIH), The Emmes Company, LLC (Industry)
• Enrollment: 112
• Locations: 8
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infection; Precancerous Condition	Biological: Gardasil	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Nov 1, 2007
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gardasil Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128.	Biological: Gardasil; week 0, 8, 24, 128; Other Names: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

Outcome Measures

Primary Outcome Measures

1. Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine [All study visits]

2. 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 [Week 28]

3. 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 [Week 28]

4. 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 [Week 28]

5. 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 [Week 28]

Secondary Outcome Measures

1. Longitudinal Changes in CD4+ Cell Count From Baseline [Week 0, 4, 12, 28]

   CD4+ cell count at week 0 was subtracted from CD4+ cell counts at each of weeks 4, 12, and 28.

2. Longitudinal Changes in Plasma HIV-1 RNA From Baseline [Week 0, 4, 12, 28]

   Plasma HIV-1 RNA at week 0 was subtracted from plasma HIV-1 RNA at each of weeks 4, 12, and 28.

3. HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status [weeks 0, 28, and 76]

4. HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status [weeks 0, 28, and 76]

5. HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status [weeks 0, 28, and 76]

6. HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status [weeks 0, 28, and 76]

7. Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series [Weeks 0, 28 and 76]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Clinical AIDS Research and Education (CARE) Center	Los Angeles	California	United States	90095-1793
2	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94143
3	Denver Health Medical Center	Denver	Colorado	United States	80204-4507
4	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
5	Montefiore Medical Center	Bronx	New York	United States	10461
6	Laser Surgery Care	New York	New York	United States	10010
7	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
8	Benaroya Research Institute at Virginia Mason Medical Center	Seattle	Washington	United States	98101

Sponsors and Collaborators

• AIDS Malignancy Consortium
• National Cancer Institute (NCI)
• The Emmes Company, LLC

Investigators

• Study Chair: Timothy J. Wilkin, MD, MPH, Weill Medical College of Cornell University
• Principal Investigator: Joel Palefsky, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AIDS Malignancy Consortium
• ClinicalTrials.gov Identifier: NCT00513526
• Other Study ID Numbers: AMC-052; CDR0000559149; U01CA121947
• First Posted: Aug 8, 2007
• Last Update Posted: Sep 17, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by AIDS Malignancy Consortium: infection; low-grade squamous intraepithelial lesion; atypical squamous cells of undetermined significance
• Additional relevant MeSH terms: Infections; Precancerous Conditions; Vaccines

Study Results

Participant Flow

Arm/Group Title	Gardasil
Arm/Group Description	Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128.
Period Title: Overall Study
STARTED	109
COMPLETED	92
NOT COMPLETED	17

Baseline Characteristics

Arm/Group Title	Gardasil
Arm/Group Description	Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128.
Overall Participants	109
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	109 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.4 (9.4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	109 100%
Region of Enrollment (participants) [Number]
United States	109 100%

Outcome Measures

1. Primary Outcome

Title	Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine
Time Frame	All study visits

Outcome Measure Data

Analysis Population Description

Intention to treat (i.e., received at least one dose of the vaccine)

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Number [participants]	0 0%

2. Primary Outcome

Title	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
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.

Arm/Group Title	Gardasil
Arm/Group Description	Number of participants seropositive for HPV-6 at week 28 among those who were seronegative at baseline.
Measure Participants	60
Number (95% Confidence Interval) [proportion of participants]	0.98 0.9%

3. Secondary Outcome

Title	Longitudinal Changes in CD4+ Cell Count From Baseline
Description	CD4+ cell count at week 0 was subtracted from CD4+ cell counts at each of weeks 4, 12, and 28.
Time Frame	Week 0, 4, 12, 28

Outcome Measure Data

Analysis Population Description

Intention to treat population, includes all participants who received at least one dose of vaccine and had assessments at week 0 and the specified week.

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Change from baseline at week 4	11
Change from baseline at week 12	9
Change from baseline at week 28	1

4. Secondary Outcome

Title	Longitudinal Changes in Plasma HIV-1 RNA From Baseline
Description	Plasma HIV-1 RNA at week 0 was subtracted from plasma HIV-1 RNA at each of weeks 4, 12, and 28.
Time Frame	Week 0, 4, 12, 28

Outcome Measure Data

Analysis Population Description

Intention to treat population, includes all participants who received at least one dose of vaccine and had assessments at week 0 and the specified week.

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Change from baseline at week 4	0
Change from baseline at week 12	0
Change from baseline at week 28	0

5. Secondary Outcome

Title	HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
Time Frame	weeks 0, 28, and 76

Outcome Measure Data

Analysis Population Description

Intent to treat population, includes all participants who received at least one dose of vaccine

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Seropositive Group at Baseline	76
Seropositive Group at Week 28	933
Seropositive Group at Week 76	613
Seronegative Group at Baseline	5
Seronegative Group at Week 28	336
Seronegative Group at Week 76	146

6. Primary Outcome

Title	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
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.

Arm/Group Title	Gardasil
Arm/Group Description	Number of participants seropositive for HPV-6 at week 28 among those who were seronegative at baseline.
Measure Participants	68
Number (95% Confidence Interval) [proportion of participants]	0.99 0.9%

7. Primary Outcome

Title	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
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.

Arm/Group Title	Gardasil
Arm/Group Description	Number of participants seropositive for HPV-6 at week 28 among those who were seronegative at baseline.
Measure Participants	62
Number (95% Confidence Interval) [proportion of participants]	1.00 0.9%

8. Primary Outcome

Title	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
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

Per protocol population for a given HPV type requires patients to be seronegative for that type at entry and to have no HPV DNA detected by PCR for that type at entry and screening. Also, patients must have received 3 doses of vaccine.

Arm/Group Title	Gardasil
Arm/Group Description	Number of participants seropositive for HPV-6 at week 28 among those who were seronegative at baseline.
Measure Participants	77
Number (95% Confidence Interval) [proportion of participants]	0.95 0.9%

9. Secondary Outcome

Title	HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
Time Frame	weeks 0, 28, and 76

Outcome Measure Data

Analysis Population Description

Intent to treat population, includes all participants who received at least one dose of vaccine

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Seropositive Group at Baseline	53
Seropositive Group at Week 28	1536
Seropositive Group at Week 76	797
Seronegative Group at Baseline	5
Seronegative Group at Week 28	503
Seronegative Group at Week 76	196

10. Secondary Outcome

Title	HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
Time Frame	weeks 0, 28, and 76

Outcome Measure Data

Analysis Population Description

Intent to treat population, includes all participants who received at least one dose of vaccine

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Seropositive Group at Baseline	83
Seropositive Group at Week 28	2005
Seropositive Group at Week 76	1225
Seronegative Group at Baseline	6
Seronegative Group at Week 28	1001
Seronegative Group at Week 76	287

11. Secondary Outcome

Title	HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status
Time Frame	weeks 0, 28, and 76

Outcome Measure Data

Analysis Population Description

Intent to treat population, includes all participants who received at least one dose of vaccine

Arm/Group Title	Gardasil
Arm/Group Description
Measure Participants	109
Seropositive Group at Baseline	53
Seropositive Group at Week 28	765
Seropositive Group at Week 76	370
Seronegative Group at Baseline	5
Seronegative Group at Week 28	181
Seronegative Group at Week 76	38

12. Secondary Outcome

Title	Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series
Time Frame	Weeks 0, 28 and 76

Outcome Measure Data

Analysis Population Description

Samples for this outcome measure were not analyzed due to loss of funding for the central lab.

Arm/Group Title	Gardasil
Arm/Group Description	Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128.
Measure Participants	0

Adverse Events

Arm/Group Title	Gardasil
Arm/Group Description	Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128.
All Cause Mortality
	Gardasil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gardasil
	Affected / at Risk (%)	# Events
Total	5/109 (4.6%)
General disorders
Pain / Head/Headache	1/109 (0.9%)	1
Pain	1/109 (0.9%)	1
Hepatobiliary disorders
Hepatobiliary/Pancreas - Other (Specify, __)	1/109 (0.9%)	1
Infections and infestations
Infection with Normal ANC or Grade 1 or 2 Neutrophils/Bone (Osteomyelitis)	1/109 (0.9%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other (Specifiy, __)	1/109 (0.9%)	2
Other (Not Including Serious) Adverse Events
	Gardasil
	Affected / at Risk (%)	# Events
Total	56/109 (51.4%)
General disorders
Fatigue (Asthenia, Lethargy, Malaise)	6/109 (5.5%)	6
Pain - Other (Specifiy, __)	6/109 (5.5%)	6
Infections and infestations
Infection - Other (Specify, __)	8/109 (7.3%)	9
Infection with Normal ANC or Grade 1 or 2 Neutrophils / Upper Airway NOS	10/109 (9.2%)	11
Infection with Unknown ANC / Upper Airway NOS	8/109 (7.3%)	9
Injury, poisoning and procedural complications
Injection Site Reaction / Extravasation Changes	35/109 (32.1%)	62
Respiratory, thoracic and mediastinal disorders
Cough	6/109 (5.5%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.