Dendritic Cell Vaccine in HIV-1 Infection

February 25, 2014 updated by: Felipe Garcia, Hospital Clinic of Barcelona

Phase II Study of Autologous Myeloid Dendritic Cells as a "Cellular Adjuvant" for a Therapeutic HIV-1 Vaccine in Early Stage HIV-1+ Patients (DCV-2).

  1. To study the efficacy of a therapeutic HIV vaccine consisting of autologous myeloid dendritic cells pulsed ex vivo with high doses of inactivated autologous HIV-1, in HIV-1 infected patients in a very early stages of the disease (CD4 > 450 x 10 6 /L).
  2. To analyze the HIV-1 humoral and cellular immune responses induced by this immune-based therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Our group has reported recently the first human trial of 4 therapeutic immunizations at six-week intervals with autologous monocyte-derived dendritic cells (MD-DC) loaded with heat-inactivated autologous HIV in 12 HIV infected patients who had been receiving highly active antiretroviral therapy (HAART) since early chronic infection. Autologous HIV was concentrated from plasma (1,500 ml) obtained by plasmapheresis after a 3-month HAART interruption (STOP1) performed 78 weeks before therapeutic immunizations, and HAART was discontinued again (STOP2) after therapeutic immunization. There was a decrease of set-point plasma viral load (PVL) >= 0.5 log after 24 weeks off HAART in 4 out of 12 patients. In addition, we observed a significant lengthening in mean doubling time of PVL rebound (p= 0.01), and significant decreases in the area under the curve of PVL rebound (p= 0.02) and in the mean peak PVL (p= 0.004) during the 12 weeks after STOP 2 compared with STOP1. This virological response was associated with a weak but significant increase in HIV-1 specific CD4 lymphoproliferative response, and with changes in HIV-1 specific CD8+ T-cell responses in peripheral blood and in lymphoid CTL cells after immunization. In lymphoid tissue, we also observed a trend towards a better control of HIV-1 replication coupled with an increase of CD4+ and CTL cells. No significant virological or immunological changes occurred in controls. We show that a therapeutic vaccine with autologous MD-DC pulsed with heat inactivated autologous HIV-1 is feasible, safe and well tolerated and elicited weak and transient cellular immune responses against HIV, associated with a partial and transient control of HIV replication in some patients.

we hypothesized that a DC vaccine pulsed with higher amount of autologous virus obtained by culture could be more effective than the vaccine we used.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clínic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmed HIV infection
  • CD4 > 450 x 10 6 /L
  • baseline VL >10,000 c/ml before any HAART
  • Part I, patients off HAART at least during 6 months
  • Part II, Patients on HAART with PVL < 200 copies/ml at least during 6 months
  • Written informed consent .

Exclusion Criteria:

  • Patients with failure to HAART
  • Patients with B or C symptoms (CDC classification 1993).
  • Age < 18 years old.
  • Pregnant or breastfeeding women
  • Patients with baseline creatinin > 2.5 mg/dl
  • Patients with baseline GOT/GPT > 250 UI/L

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pulsed dendritic cells untreated patients
Untreated patients receiving a dendritic cell based vaccine pulsed with autologous heat iactivated virus
Biological: Dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Placebo Comparator: non pulsed dendritic cells untreated patients
Biological: non pulsed dendritic cell untreated patients
107 DC subcutaneous 3 doses every 2 weeks
Active Comparator: pulsed dendritic cell treated patient
treated patients will be immunized with a dendritic cell vaccine pulsed with heat inactivated autologous virus immediately before art interruption
Biological: pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Active Comparator: pulsed dendritic cell in treated patients
patients will be immunized with a dendritic cell vaccine pulsed with heat inactivted autologous virus immediately after interruption of art
Biological: dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
Placebo Comparator: non pulsed dendritic cells
Biological: non pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART.
Time Frame: 6 and 12 months
6 and 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion with evidence of HIV-specific CTL comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
Time Frame: 6 and 12 months
6 and 12 months
Proportion with evidence of HIV-specific T-cell proliferative response comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
Time Frame: 6 and 12 months
6 and 12 months
Proportion with evidence of HIV-specific neutralizing activity of serum comparing end of immune-based therapy, and end of trial (week 48) with start of immune-based therapy.
Time Frame: 6 and 12 months
6 and 12 months
HIV-1 specific CTL responses in lymphoid tissue
Time Frame: 0 and 6 months
0 and 6 months
DC Migration
Time Frame: 0 and 2 weeks
0 and 2 weeks
Viral load in semen and vaginal secretions
Time Frame: 0 and 6 months
0 and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Clinic of Barcelona

Investigators

  • Principal Investigator: Felipe García, MD, PhD, Hospital Clínic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

November 17, 2006

First Submitted That Met QC Criteria

November 17, 2006

First Posted (Estimate)

November 22, 2006

Study Record Updates

Last Update Posted (Estimate)

February 26, 2014

Last Update Submitted That Met QC Criteria

February 25, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DCV-02/MANON07

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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