CAR-T Cells for HIV Infection

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a limited-center, open-label dose escalating phase I/IIa study of autologous T cells expressing LVgp120duoCAR molecules in people with HIV infection. It will follow a 3+3 design. Dose escalation decisions will be made when a minimum of three participants have completed the safety-evaluation period (45 days) at a given dose level. Cohort 1 will undergo infusion of a single low-dose regimen of LVgp120duoCAR-T cells. Cohort 2 will undergo non-ablative conditioning with cyclophosphamide, followed by infusion of a single low-dose regimen of LVgp120duoCAR-T cells. Cohort 3 will undergo non-ablative conditioning with cyclophosphamide, followed infusion of a single high-dose regimen of LVgp120duoCAR-T cells. Following administration of the experimental therapy, HIV medications will be paused for participants in each group during an analytic treatment interruption.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Steven Deeks
• Collaborator: Caring Cross
• Treatments: Cyclophosphamide

Criteria

Inclusion Criteria:

• Male or female, age ≥ 18 and ≤ 65 years

• HIV-1 infection

• On continuous antiretroviral therapy for at least 12 months without any interruptions of greater than 14 consecutive days, and on a stable regimen that does not include a non-nucleoside reverse transcriptase inhibitor (NNRTI) for at least 4 weeks or any long-acting ART drug that may be active in the participant after ART interruption for up to one year, without plans to modify ART during the study period

• Screening plasma HIV RNA levels below the limit of quantification on all available determinations in past 12 months (isolated single values ≥ 40 but < 200 copies/mL will be allowed if they were preceded and followed by undetectable viral load determinations)

• CD4+ T cell count nadir > 300 cells/mm3

• Screening CD4+ T-cell count ≥ 500 cells/mm3

• Available ART treatment history and the capacity to construct an effective antiretroviral treatment regimen

• Willing to pause ART as part of the study

Exclusion Criteria:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study

• ART regimen that includes a long-acting anti-HIV drug and/or NNRTI that may be active in the participant for up to one year after ART interruption

• ART regimen that includes protease inhibitor(s) and/or AZT. These drugs may increase the toxicity of cyclophosphamide.

• Any history of an HIV-associated malignancy, including Kaposi's sarcoma and any type of lymphoma, or virus-associated cancers

• History of or current active hepatitis B (HBV) infection defined as positive HBV surface antigen test. A positive anti-HBc regardless of HBsAg status.

• Active hepatitis C (HCV) infection

• Active or latent tuberculosis infection

• Chronic liver disease

• Active and poorly controlled atherosclerotic cardiovascular disease

• Unwillingness to abstain from sex or use barrier protection for any sexual activity during the treatment interruption.