Clinical trial NCT00510497: Autologous Dendritic Cell Vaccine in HIV1 Infection
Official title: Phase I/II Evaluation of Therapeutic Immunization With Autologous Dendritic Cells Pulsed With Autologous, Inactivated HIV-1 Infected, Apoptotic Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: dendritic cell
therapeutic vaccine
HIV-1
apoptotic cells
Phase I/II
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2007-08-02
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aims to look at the safety and tolerability of immunization with dendritic cell vaccine prepared using the patient's own cells and virus. It also aims to explore the virologic efficacy of the vaccine as determined by a decrease in the viral load 12 weeks after analytic treatment interruption.

Detailed description: This is a phase I/II, open label, single-arm, single-site clinical trial designed to evaluate the safety and antiviral activity of the ApB DC vaccine, a therapeutic vaccine derived from autologous dendritic cells loaded with autologous HIV-1 infected apoptotic cells. The study will be conducted in three phases. The first is the pre-vaccination phase that includes study entry, isolation of autologous virus, and initiation of antiretroviral therapy. Once the patient's viral load has been suppressed to undetectable levels (\<50 copies/mL) and sufficient virus has been isolated, the second phase will begin. This includes leukapheresis in order to harvest monocytes and lymphocytes necessary for vaccine preparation. Three vaccine doses will be administered subcutaneously every other week. Six weeks after the last vaccination, the third phase, analytic treatment interruption (ATI) phase, will begin. A fourth, booster dose of vaccine will be given two weeks after the start of treatment interruption. The treatment interruption will be continued for twelve weeks after which the primary HIV provider will decide whether or not antiretroviral therapy should be restarted. CD4 and viral load will be closely monitored throughout the study especially during treatment interruption. Follow-up will be continued for 24 weeks after the 12-week treatment interruption.

Eligibility criteria: Inclusion Criteria:

* Confirmed HIV-1 infection.
* CD4 greater than or equal to 350 cells/mL within 8 weeks prior to study entry.
* Plasma HIV-1 RNA level of 5000-100,000 copies/mL within 8 weeks prior to study entry.
* Antiretroviral therapy naive.
* Willingness to interrupt ART for at least 12 weeks.
* Written informed consent.

Exclusion Criteria:

* Treatment within 30 days prior to study entry with systemic steroids or other immunosuppressives, or any underlying disease which may require use of such medications during the study period.
* Receipt of any vaccinations other than routine ones within 6 months of study entry
* Pregnancy or breastfeeding
* Previous or current CDC Category C event
* Receipt of any investigational product within 12 weeks prior to study entry.

Primary outcomes:
measure: Safety and Tolerability of Autologous HIV-1 ApB DC Vaccine.
timeFrame: 80 weeks
Secondary outcomes:
measure: Virologic Efficacy (HIV-1 Viral Load at End of ATI Minus Viral Load Prior to ART)
timeFrame: at the end of 12 weeks treatment interruption
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Sharon A Riddler, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Macatangay BJ, Riddler SA, Wheeler ND, Spindler J, Lawani M, Hong F, Buffo MJ, Whiteside TL, Kearney MF, Mellors JW, Rinaldo CR. Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic Cells. J Infect Dis. 2016 May 1;213(9):1400-9. doi: 10.1093/infdis/jiv582. Epub 2015 Dec 8.
citation: Whiteside TL, Piazza P, Reiter A, Stanson J, Connolly NC, Rinaldo CR Jr, Riddler SA. Production of a dendritic cell-based vaccine containing inactivated autologous virus for therapy of patients with chronic human immunodeficiency virus type 1 infection. Clin Vaccine Immunol. 2009 Feb;16(2):233-40. doi: 10.1128/CVI.00066-08. Epub 2008 Nov 26.