Clinical trial
A Pilot Study to Evaluate the Feasibility and Safety of Cytomegalovirus-Specific, Anti-HIV Chimeric Antigen Receptor (CMV-HIV CAR) T Cells in People Living With HIV
Name
22508
Description
Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIVCAR T cells) may provide a safe and effective way to eliminate HIV-infected cells.
However, the number of HIV-infected cells is low in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of HIV-1-infected individuals are CMV-seropositive and CMV-specific T cells have been shown to persist. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human Phase 1, open-label, single-arm study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH), and achieve long-term remission in the presence of ART.
Trial arms
Trial start
2024-07-30
Estimated PCD
2026-03-30
Trial end
2028-03-30
Status
Not yet recruiting
Phase
Early phase I
Treatment
CMV/HIV-CAR T Cells
Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cewll manufacturing. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV)infusion of autologous CMV/HIV-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.
Arms:
Dose Level +1, Dose Level +2, Dose Level -1
Size
15
Primary endpoint
Dose limiting toxicities (DLT)
Up to 28 days after the infusion
Toxicity profile
Up to 28 days after the infusion
Eligibility criteria
Inclusion Criteria:
* Participant must be ≥ 18 years of age at the time of screening;
* Karnofsky Performance Status (KPS) ≥ 70;
* Documented HIV-1 infection anytime prior to study entry.;
* On stable ART with undetectable HIV-1 RNA (i.e \< 20 copies /mL) for at least 48 weeks prior to screening (2 plasma HIV-1 RNA blips 25-200 copies/mL are allowable);
* CD4+ cell count ≥ 450 cells/μL;
* Adequate organ function;
* Willingness to interrupt ART regimen for 4 days prior to leukapheresis;
* Not pregnant or breastfeeding.
Exclusion Criteria:
* Concurrent illness or comorbid condition;
* History of resistance to two or more classes of antiretroviral drugs;
* History of prior receipt of an experimental HIV-1, immunotherapeutic agent, or gene therapy product.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 15, 'type': 'ESTIMATED'}}
Updated at
2024-04-25
1 organization
1 product
1 indication
Organization
City of Hope Medical CenterProduct
CMV/HIV-CAR T CellsIndication
HIV-1