Last updated on January 2019

Study to Evaluate Effects of Vorinostat and HXTC on Persistent HIV-1 Infection in HIV-Infected Subjects Started on ART

Brief description of study

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 cART. 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 cART regimen throughout the study.

Detailed Study 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: HIV-infected men and women, 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 cART and have a CD4 count 350 cells/mm3. We plan to enroll up to 12 participants at 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 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 QVOA assay threshold, and 2. Exhibit ex-vivo (Step

  1. response to VOR

Participants progressing to Step 2 will receive 2 (two) doses 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.

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, the first infusion in Step 5 (HXTC #3) will be omitted.

Following the final HXTC infusion in Step 5, participants move into Step 6 for a minimum of six (6) additional visits: 21, 22, 23, 24, 25, and 26. The 3rd and final leukapheresis will occur at Visit 23 (Week 21), approximately 9 weeks after the last HXTC infusion to evaluate the effect of study treatment on IUPM by QVOA.

All participants who receive greater than 8 doses of VOR in the study 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 is created because of genotoxic findings that were associated with the use of VOR. All participants will be monitored for development of future malignancies.

Clinical Study Identifier: NCT03212989

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