Vaccination of HIV-1 Infected Patients With Dendritic Cells in Addition to Antiretroviral Treatment - (DALIA Trial)

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)

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Biological: Dendritic Cell Vaccine

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).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor University Medical Center

Participation Criteria

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dendritic Cell Vaccine; Autologous dendritic cells generated using GM-CSF and interferon alpha, loaded with HIV lipopeptides and activated with lipopolysaccharide

Biological: Dendritic Cell Vaccine; Biological/Vaccine: Experimental: Dendritic Cell Vaccine Patients will receive 4 doses of the vaccine at weeks 0, 4, 8 and 12. The vaccine will be injected subcutaneously, in 3 separate injection sites in the upper and lower extremities. At week 24, patients will have HAART treatment interrupted. The HAART treatment will be resumed at week 48 or earlier at any time point if one of the following occur: two consecutive measurements of CD4+ T cell count below 350x10e6 cells/L and/or 25% of total lymphocytes within at least a 2 weeks; an opportunistic infection; a CDC class C-defining event (defined in appendix 2); a serious non-AIDS defining event. Patients will have follow-up visits on weeks: 22, 24, 25, 26, 27, 28, 32, 36, 40, 44, and 48.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	May 2010

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate immune responses using several defined assays as well as viral and CD4+ T cell status	May 2010

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Collaborators: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Principal Investigator: Jacques Banchereau, PhD, Baylor Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: November 21, 2008
• First Submitted That Met QC Criteria: November 21, 2008
• First Posted (Estimate): November 24, 2008

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Vaccine; AIDS; HAART; Dendritic Cells; DALIA
• Other Study ID Numbers: 008-017