Study to Evaluate Effects of Vorinostat and HXTC on Persistent HIV-1 Infection in HIV-Infected Subjects Started on Antiretroviral Therapy (ART)
Condition: HIV-1 Infection
MeSH terms: Infections; Communicable Diseases; HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I, single-site, study to evaluate the effects of VOR and HIV-1 Antigen
      Expanded Specific T Cell Therapy (HXTC) on persistent HIV-1 Infection in HIV-infected
      individuals suppressed on ART. Twelve participants with durable viral suppression will be
      enrolled and will complete the study. All participants will receive the same treatment and if
      eligible, will be dosed with HXTC and VOR. Participants will continue their baseline ART
      regimen throughout the study.
    

Detailed description: 
      Purpose: This study will test the use of special immune system cells called expanded
      HIV-specific T Cell (HXTC) Therapy to stimulate the immune system to respond better to HIV.
      HXTC Therapy will be given in combination with the drug Vorinostat (VOR) which has been shown
      to stimulate some cells infected with HIV to become active and start making HIV virus. The
      purpose of this study is to:

        1. Evaluate the safety of a series of HXTC infusions in combination with serial doses of
           VOR and

        2. Help scientists evaluate ways of re-activating latent (non-active) HIV virus and
           determine if the immune system can be made stronger to eliminate the activated HIV
           virus.

      Participants: Men and women living with HIV, ≥ 18 and < 65 years of age, with durable viral
      suppression for ≥ 24 months as measured on standard HIV RNA assays. Eligible participants
      must be on stable combination ART (cART) and have a CD4 count ≥ 350 cells/mm3. We plan to
      enroll up to 12 participants at the University of North Carolina at Chapel Hill (UNC) who
      complete all 6 Steps of this study.

      Procedures (methods):

      In Step 1 and prior to initiating the two series of VOR and HXTC combined therapies, all
      participants will undergo study screening and enrollment where they will be required to: 1.
      Demonstrate a baseline measurement of the frequency of resting CD4 T cell infection ≥ 0.3
      infected cells per million as determined by QVOA, as a further decrease from this low
      frequency of infection cannot be definitively measured given the quantitative viral outgrowth
      assay (QVOA) threshold.

      Participants with an infectious cells per million (IUPM) measurement > or equal to 0.3 will
      provide whole blood cells for the manufacture of their HXTC product (Step 3). Successful
      manufacturing of the HIV-1 antigen expanded specific T cells will progress participants to
      combination treatment in Steps 4 and 5. In Steps 4 and Step 5, participants will receive two
      series of VOR dosing and HXTC infusions, for a total 20 doses of VOR 400 mg and 5 HXTC
      infusions.

      In the first series (Step 4), participants will receive VOR 400 mg PO every 72 hours for 10
      doses and 2 infusions of HXTC. The first HXTC infusion will be administered six hours after
      the first dose of VOR (HXTC #1) and the 2nd HXTC infusion (HXTC #2) will occur 6 hours after
      the 6th dose of VOR.

      In the second series in Step 5, participants will receive an additional 10 doses of VOR 400
      mg PO every 72 hours and 3 HXTC infusions. The first HXTC infusion in Step 5 (HXTC #3) will
      occur 6 hours after the 11th dose of VOR (1st dose in Step 5), the 2nd HXTC infusion (HXTC
      #4) will occur 6 hours after the 16th dose of VOR, and the 3rd HXTC infusion (HXTC #5) will
      occur 1 - 3 days after the 20th dose of VOR.

      If there are insufficient cells manufactured to allow 5 infusions at 1 x 10-8 cells/m-2 dose,
      the dose will be adjusted to allow 5 infusions at a dose > or equal to 5 x 10-7 cells/m-2 but
      < 1 x 10-8 cells/m-2 dose.

      Following the final HXTC infusion, participants move into Step 6 for a minimum of six
      additional visits: 21-26. The 2nd leukapheresis will occur at Visit 23 (Week 21),
      approximately 9 weeks after the last HXTC infusion to evaluate the effect of study treatment
      on the IUPM by QVOA.

      All participants who receive greater than 8 doses of VOR (3200 mg) will be required to enter
      a study cancer registry where they will be contacted once a year for 5 years after completion
      of their study participation. The registry was created to monitor participants for the
      development of future malignancies given concern for genotoxic impact with the use of VOR.
    

Intervention name(s): Vorinostat; HXTC
Intervention type(s): Drug; Biological
Intervention description(s): Participants meeting criteria for Step 1 (exhibit ex-vivo response to VOR) will progress to Step 2 where they will receive a single dose of VOR 400 mg followed by a leukapheresis. If an increase in cell-associated HIV RNA (ca-RNA) is observed in-vivo following the single VOR dose, they will be eligible to donate cells for the manufacture of HXTC (Step 3). Successful manufacturing of the HIV-1 antigen expanded specific T cells will progress participants to combination treatment in Steps 4 and 5. In Steps 4 and Step 5, participants will receive two series of VOR dosing and HXTC infusions, for a total 20 doses of VOR 400 mg and 5 HXTC infusions.; Participants meeting criteria for Step 1 (exhibit ex-vivo response to VOR) will progress to Step 2 where they will receive a single dose of VOR 400 mg followed by a leukapheresis. If an increase in cell-associated HIV RNA (ca-RNA) is observed in-vivo following the single VOR dose, they will be eligible to donate cells for the manufacture of HXTC (Step 3). Successful manufacturing of the HIV-1 antigen expanded specific T cells will progress participants to combination treatment in Steps 4 and 5. In Steps 4 and Step 5, participants will receive two series of VOR dosing and HXTC infusions, for a total 20 doses of VOR 400 mg and 5 HXTC infusions.
Other intervention name(s): ZOLINZA; MK-0683; SAHA; HIV-1 antigen expanded specific T-cell
Intervention MeSH terms: Vorinostat
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV; HXTC; Antiretroviral Therapy; HIV-Infected; Vorinostat; AIDS