Study to Evaluate Effects of Vorinostat and HXTC on Persistent HIV-1 Infection in HIV-Infected Subjects Started on Antiretroviral Therapy (ART) — XTRA  

HIV-1 Infection Clinical Trial

Official title: IGHID 11627 - A Phase I Study to Evaluate the Effects of Vorinostat and HIV-1 Antigen Expanded Specific T Cell Therapy (HXTC) on Persistent HIV-1 Infection in HIV-Infected Individuals Started on Antiretroviral Therapy (The XTRA Study)

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• HIV-1 Infection
• Infections

• NCT number: NCT03212989
• Study type: Interventional
• Source: University of North Carolina, Chapel Hill
• Status: Completed
• Phase: Phase 1
• Start date: June 27, 2017
• Completion date: July 5, 2022