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| Name | Class |
|---|---|
| Caring Cross | UNKNOWN |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose CAR-T Cells Only | Experimental | 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. |
|
| Conditioning + Low Dose CAR-T Cells | Experimental | 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. |
|
| Conditioning + High Dose CAR-T Cells | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | Non-ablative conditioning with cyclophosphamide. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants reporting a new Grade 3 or greater adverse event that is definitely, probably, or possibly related to study treatment within 1 year of product administration. | The primary safety outcome will be the number of participants reporting a new Grade 3 or greater adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, including signs/symptoms, lab toxicity or clinical event, that is definitely, probably, or possibly related to study treatment within 1 year of product administration. | Within 1 year of product administration |
| Number of participants achieving post-treatment control within 36 weeks of product administration. | The primary efficacy outcome will be the proportion of individuals who achieve study-defined post-treatment control. The investigators will define post-treatment control in two ways. First, participants who fail to show any consistent rebound above 400 copies RNA/mL between Weeks 12 and Week 36 will be considered as having achieved post-treatment control. Second, participants who exhibit a rebound and eventually achieve 24 weeks of virus control will be considered as having achieved post-treatment control. | Week 36 |
| Measure | Description | Time Frame |
|---|---|---|
| Persistence of LVgp120duoCAR-T cells in blood during therapy | Real-time quantitative polymerase chain reaction (qPCR) will be used to monitor the frequency of circulating CD4+ and CD8+ T cells harboring the integrated LVgp120duoCAR-T gene longitudinally to determine product persistence. This measure will be performed on blood samples. | Week 12 through Week 36 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rebecca Hoh | Contact | 415-476-4082 | 139 | rebecca.hoh@ucsf.edu |
| Name | Affiliation | Role |
|---|---|---|
| Steven Deeks, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Davis | Recruiting | Sacramento | California | 95817 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36345941 | Derived | 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. |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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The clinical trial is an open-label dose escalating phase I/IIa study of autologous T cells expressing LVgp120duoCAR molecules that target and kill HIV-1 gp120 expressing cells. Participants will be enrolled sequentially in up to three sequentially enrolled cohorts in 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. There are 3 dose escalation cohorts with the first 3 participants starting at Cohort 1.
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| LVgp120duoCAR-T cells, low dose | Biological | A single dose of 3 x 10^5 cells/kg LVgp120duoCAR-T cells will be infused. |
|
| LVgp120duoCAR-T cells, high dose | Biological | A single dose of 1 x 10^6 cells/kg LVgp120duoCAR-T cells will be infused. |
|
| Analytic Treatment Interruption | Other | HIV antiretroviral therapy medications will be paused. |
|
| Persistence of LVgp120duoCAR-T cells in tissues during therapy | Real-time quantitative polymerase chain reaction (qPCR) will be used to monitor the frequency of circulating CD4+ and CD8+ T cells harboring the integrated LVgp120duoCAR-T gene longitudinally to determine product persistence. This measure will be performed on tissue samples collected from volunteers agreeing to lymph node sampling. | Week 12 through Week 36 |
| Change in quantitative virologic measures of the HIV reservoir pre- and post-therapy | The HIV reservoir will be measured using methods such as quantitative PCR (qPCR), ultra-sensitive PCR, and/or the intact proviral DNA assay (IPDA) at baseline and time points throughout the study. Changes in the number of copies per 10^6 T cells will be reported. | Baseline and 36 weeks |
| Zuckerberg San Francisco General | Recruiting | San Francisco | California | 94110 | United States |
|
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D012897 | Slow Virus Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |