RecruitingPhase 1Phase 2NCT04648046

CAR-T Cells for HIV Infection

Safety and Anti-HIV Activity of Autologous CD4+ and CD8+ T Cells Transduced With a Lentiviral Vector Encoding Bi-specific Anti-gp120 CAR Molecules (LVgp120duoCAR-T) in Anti-retroviral Drug-treated HIV-1 Infection

Sponsor

Steven Deeks

Enrollment

18 participants

Start Date

Mar 1, 2021

Study Type

INTERVENTIONAL

Conditions

HIV Infections

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.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria8

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 Criteria10

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.