Clinical trial NCT00796770: Vaccination of HIV-1 Infected Patients With Dendritic Cells in Addition to Antiretroviral Treatment - (DALIA Trial)
Official title: Vaccination of HIV-1 Infected Patients With Ex-vivo Generated Interferon-α Dendritic Cells Loaded With HIV-1 Lipopeptides and Activated With Lipopolysaccharide in Addition to Antiretroviral Treatment: Exploratory Phase I Study-(DALIA Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Keywords: HIV
Vaccine
HAART
HIV-1
AIDS
Dendritic Cells
DALIA
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
Collaborators: name: French National Agency for Research on AIDS and Viral Hepatitis
First posted: 2008-11-24
Enrollment: 19
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: The purpose of this study is to determine whether the administration of a dendritic cell vaccine is a safe and effective treatment for HIV-1 patients.

Detailed description: The purpose of this study is to determine whether the administration of a dendritic cell vaccine is a safe and effective treatment for HIV-1 patients. This will be a phase I, single-center, study in HIV infected patients. The primary objective is to evaluate safety of the vaccination schedule (from apheresis procedure to week 24) at week 24 and safety of the Analytical Treatment Interruption (ATI; from week 24 to week 48) at week 48 in HIV-1 infected patients who have been receiving antiretroviral therapy for at least 12 months with HIV-1 RNA ≤50 copies/mL and CD4+ T cell counts \>500/mm3 at entry in the trial and who received, in addition to anti-retroviral therapy for 24 weeks, vaccination with ex vivo generated interferon-alpha dendritic cells loaded with HIV-1 lipopeptides and activated with lipopolysaccharide (BIIR/ANRS-HIVax-001, the DC vaccine product).

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 years old
2. written informed consent
3. HIV1 infection documented by any licensed ELISA test kit and confirmed by Western Blot at anytime prior to study entry
4. on treatment with a combination of antiviral drugs (HAART) for at least 12 months, and stable on treatment for at least 3 months prior to enrollment. HAART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral drugs (other than 3 Nucs only and low dose ritonavir used for boosting other protease inhibitors does not count as one of these three antiretroviral agents)
5. CD4+ T cell counts \> 500 cells/mm3 on at least two consecutive measurements (including the screening value) within the previous 6 months prior to enrollment (occasional CD4 cell counts ranging between 450-500 cells/mm3 is permitted)
6. nadir CD4+ T cell counts \> 300 cells/mm3 prior HAART
7. plasma HIV-RNA ≤ 50 copies/mL on at least two consecutive measurements (including the screening value) within the previous 3 months prior to enrollment (occasional so called 'blips' up to 200 copies/mL are permitted)
8. no history of CDC class C event (Appendix 2)
9. no vaccination in the last 3 months
10. blood cells and chemistry:

    1. neutrophils ≥ 1,000/mm3
    2. platelets ≥ 100,000/mm3
    3. hemoglobin ≥ 10 g/dl
    4. creatinin ≤ 1.5 x N
    5. ASAT, ALAT, conjugated bilirubin ≤ 2.5 x N
11. Adequate Kidney Function proteinuria ≤ 1 g/l (++)by urinalysis

Exclusion Criteria:

1. Nadir CD4+ T cell counts \< 300 cells/mm3 prior HAART
2. pregnant or lactating woman
3. any prior chemotherapy treatment
4. interferon alpha (IFN-α-2b) or sargramostim (GM-CSF) \< 12 weeks before the beginning of the trial
5. interleukin-2 (IL-2) \<12 weeks before the beginning of the trial,
6. corticosteroids or other immunosuppressive agents \<12 weeks before beginning the trial
7. active asthma and/or on treatment for asthma,
8. any history of malignancy (except basal carcinoma of the skin) including any hematologic malignancy or AIDS defining malignancy, such as lymphoproliferative disorder or Kaposi's sarcoma. Patients with Kaposi's sarcoma limited to the skin that disappeared while on HAART therapy, and without requiring any other systemic therapy, 1 year prior to study entry will be eligible to participate
9. angina pectoris or with congestive heart failure, with auto-immune disease, or evolutive pulmonary disease, or organ failure
10. active infections including viral hepatitis
11. history of thrombocytopenia
12. chronic hepatitis B or C
13. previous exposure to any HIV experimental vaccine.

Primary outcomes:
measure: To evaluate the safety of the vaccination schedule at week 24 and the safety of the Analytical Treatment Interruption at week 48 in HIV-1 infected patients.
timeFrame: May 2010
Secondary outcomes:
measure: To evaluate immune responses using several defined assays as well as viral and CD4+ T cell status
timeFrame: May 2010
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: Baylor Research Institute
name: Jacques Banchereau, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cobb A, Roberts LK, Palucka AK, Mead H, Montes M, Ranganathan R, Burkeholder S, Finholt JP, Blankenship D, King B, Sloan L, Harrod AC, Levy Y, Banchereau J. Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine. J Immunol Methods. 2011 Feb 28;365(1-2):27-37. doi: 10.1016/j.jim.2010.11.002. Epub 2010 Nov 18.