Dendritic Cell Vaccine in HIV-1 Infection

HIV Infections Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00402142
• Other study ID #: DCV-02/MANON07
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 17, 2006
• Last updated: February 25, 2014
• Start date: November 2006
• Est. completion date: December 2011

Study information

• Verified date: February 2014
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Infection

Intervention

Biological:
• Dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
• non pulsed dendritic cell untreated patients
107 DC subcutaneous 3 doses every 2 weeks
• pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
• dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks
• non pulsed dendritic cell vaccine
107 DC subcutaneous 3 doses every 2 weeks

Locations

Country	Name	City	State
Spain	Hospital Clínic	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

Country where clinical trial is conducted

Spain, 

References & Publications (3)

García F, Climent N, Assoumou L, Gil C, González N, Alcamí J, León A, Romeu J, Dalmau J, Martínez-Picado J, Lifson J, Autran B, Costagliola D, Clotet B, Gatell JM, Plana M, Gallart T; DCV2/MANON07- AIDS Vaccine Research Objective Study Group. A therapeuti — View Citation

García F, Climent N, Guardo AC, Gil C, León A, Autran B, Lifson JD, Martínez-Picado J, Dalmau J, Clotet B, Gatell JM, Plana M, Gallart T; DCV2/MANON07-ORVACS Study Group. A dendritic cell-based vaccine elicits T cell responses associated with control of H — View Citation

García F, Lejeune M, Climent N, Gil C, Alcamí J, Morente V, Alós L, Ruiz A, Setoain J, Fumero E, Castro P, López A, Cruceta A, Piera C, Florence E, Pereira A, Libois A, González N, Guilá M, Caballero M, Lomeña F, Joseph J, Miró JM, Pumarola T, Plana M, Gatell JM, Gallart T. Therapeutic immunization with dendritic cells loaded with heat-inactivated autologous HIV-1 in patients with chronic HIV-1 infection. J Infect Dis. 2005 May 15;191(10):1680-5. Epub 2005 Apr 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of steady state viremia (so-called viral set point) after 6-12 months after vaccination with viremia before HAART.		6 and 12 months	Yes
Secondary	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.		6 and 12 months	No
Secondary	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.		6 and 12 months	No
Secondary	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.		6 and 12 months	No
Secondary	HIV-1 specific CTL responses in lymphoid tissue		0 and 6 months	No
Secondary	DC Migration		0 and 2 weeks	No
Secondary	Viral load in semen and vaginal secretions		0 and 6 months	No