CAR-T Cells for HIV Infection

NCT ID: NCT04648046

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2029-12-31

Brief 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.

Detailed Description

A limited-center, open-label dose escalating phase I/IIa study of autologous T cells expressing LVgp120duoCAR molecules will be performed. Participants will be enrolled sequentially in up to three cohorts following 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. No dose escalation will be allowed in an individual participant, and participants who have dose limiting adverse events will reinstate ART therapy at first available opportunity.

Following a 3+3 design, each cohort will enroll at least 3 participants. If there are no safety issues with dosing in a cohort, the investigators will proceed to the following cohort. If one participant in a cohort experiences a safety issue, an additional 3 individuals will be enrolled in that cohort to assess safety prior to proceeding to the next cohort. See below for Dose Escalation Procedures.

The first 3 participants start at Cohort 1. Data from Cohort 1 will be submitted for FDA review prior to dosing Cohorts 2 and 3 to determine if cyclophosphamide conditioning is needed.

Cohort 1: Participants will NOT undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 105 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion.

Cohort 2: Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 105 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion.

Cohort 3: Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 1 x 106 cells/kg LVgp120duoCAR-T cells will be infused into the participant. ART will be interrupted immediately after infusion.

Dose Escalation Procedures:

1. If, after 45 days of study treatment, no participant out of the initial 3 in a cohort exhibits a study treatment-related DLT, then the next cohort of participants will be treated at the subsequent cohort.

2. If, after 45 days of study treatment, 1 participant out of the initial 3 in a cohort exhibits a study treatment-related DLT, then up to 3 additional participants will be added at that dose level.

3. If no additional participant develops a study treatment-related DLT (i.e., 1/6 participants with DLT at that dose level), then the next cohort of participants will be treated at the next higher dose level.

4. However, if a second participant develops a study treatment-related DLT, even if it is before there are 6 total participants on that level, then the maximum tolerated dose (MTD) has been exceeded and no additional participants should be added to this or any higher doses. A total of 6 participants should then be treated on the next lowest dose level to ensure its tolerability and to better define the MTD. Thus, the MTD is defined as the highest assigned dose level at which < 2/6 participants have a DLT.

5. If 2 participants in Cohort 1 experience a related DLT, the MTD will have been exceeded and no additional participants will be added at any higher level.

6. If the investigators experience DLTs in Cohort 1, the investigators will de-escalate the dose to 1 x 10^5 cells per kg. If the investigators experience DLTs at the de-escalated dose of 1 x 10^5 cells per kg, the study will stop.

Conditions

HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose CAR-T Cells Only

Participants will NOT undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion.

Group Type: EXPERIMENTAL

LVgp120duoCAR-T cells, low dose

Intervention Type: BIOLOGICAL

A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused.

Analytic Treatment Interruption

Intervention Type: OTHER

HIV antiretroviral therapy medications will be paused.

Conditioning + Low Dose CAR-T Cells

Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused. ART will be interrupted immediately after infusion.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Non-ablative conditioning with cyclophosphamide.

LVgp120duoCAR-T cells, low dose

Intervention Type: BIOLOGICAL

A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused.

Analytic Treatment Interruption

Intervention Type: OTHER

HIV antiretroviral therapy medications will be paused.

Conditioning + High Dose CAR-T Cells

Participants will undergo non-ablative conditioning with cyclophosphamide. A single dose of 1 x 10\^6 cells/kg LVgp120duoCAR-T cells will be infused into the participant. ART will be interrupted immediately after infusion.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Non-ablative conditioning with cyclophosphamide.

LVgp120duoCAR-T cells, high dose

Intervention Type: BIOLOGICAL

A single dose of 1 x 10\^6 cells/kg LVgp120duoCAR-T cells will be infused.

Analytic Treatment Interruption

Intervention Type: OTHER

HIV antiretroviral therapy medications will be paused.

Interventions

Cyclophosphamide

Non-ablative conditioning with cyclophosphamide.

Intervention Type: DRUG

LVgp120duoCAR-T cells, low dose

A single dose of 3 x 10\^5 cells/kg LVgp120duoCAR-T cells will be infused.

Intervention Type: BIOLOGICAL

LVgp120duoCAR-T cells, high dose

A single dose of 1 x 10\^6 cells/kg LVgp120duoCAR-T cells will be infused.

Intervention Type: BIOLOGICAL

Analytic Treatment Interruption

HIV antiretroviral therapy medications will be paused.

Intervention Type: OTHER

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Caring Cross

UNKNOWN

Sponsor Role: collaborator

Steven Deeks

OTHER

Sponsor Role: lead

Responsible Party

Steven Deeks

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Steven Deeks, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, Davis

Sacramento, California, United States

Site Status: RECRUITING

Zuckerberg San Francisco General

San Francisco, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rebecca Hoh

Role: CONTACT

rebecca.hoh@ucsf.edu

415-476-4082 ext. 139

Facility Contacts

Christina Dyner, RN

Role: primary

cjdyer@ucdavis.edu

Rebecca Hoh, MS

Role: primary

rebecca.hoh@ucsf.edu

(415) 476-4082 ext. 139

References

Anthony-Gonda K, Ray A, Su H, Wang Y, Xiong Y, Lee D, Block A, Chilunda V, Weiselberg J, Zemelko L, Wang YY, Kleinsorge-Block S, Reese JS, de Lima M, Ochsenbauer C, Kappes JC, Dimitrov DS, Orentas R, Deeks SG, Rutishauser RL, Berman JW, Goldstein H, Dropulic B. In vivo killing of primary HIV-infected cells by peripheral-injected early memory-enriched anti-HIV duoCAR T cells. JCI Insight. 2022 Nov 8;7(21):e161698. doi: 10.1172/jci.insight.161698.

Reference Type: DERIVED

PMID: 36345941 (View on PubMed)

Other Identifiers

20-31976

Identifier Type: -

Identifier Source: org_study_id