CD4-ZETA Gene Modified T Cells With and Without Exogenous Interleukin-2 (IL-2) In HIV Patients

Study Overview
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Brief Summary
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The purpose of this study is to find out the safety and activity of an experimental anti-HIV treatment using autologous CD4-zeta gene-changed T cells and/or IL-2 (recombinant interleukin2).

Detailed Description
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The purpose of this study is to find out the safety and activity of an experimental anti-HIV treatment using autologous CD4-zeta gene-changed T cells and/or IL-2 (recombinant interleukin2). The treatments that the investigators are studying try to improve the immune system by changing some of your T cells so they can find and destroy HIV infected cells (HIV is usually able to hide from your T cells). In this study, the investigators are also trying to find out if giving you more IL-2 at the same time as gene changed T cells will help the T cells to live longer or fight HIV better.

Official Title
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A Phase I/II Study Of the Safety, Survival, and Trafficking of Autologous CD4-ZETA Gene-Modified T Cells With and Without Extension Interleukin-2 in HIV Infected Patients

Conditions
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HIV-1 Infections

Intervention / Treatment
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* Drug: HAART
* Biological: T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DOD beneficiary with HIV-1 infection Greater than or equal to 200 CD4 cells/mm3 Undetectable viral load, for at least the previous 8 weeks Stable anti-retroviral regimen for greater than or equal to 8 weeks Venous access sufficient for apheresis Karnofsky performance > 80% Exclusion Criteria: Inadequate organ function Lifetime history of CD4 count less than 200 cells/mm3 on 2 consecutive measurements over at least an 8 week period Any previous history of gene therapy Recent IL-2 therapy or other treatment with an investigational agent Pregnancy some medications (hydroxyurea, corticosteroids and other immunosuppressants, chemotherapy, etc.)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM 1<br>Arm I (N=5) received antiretroviral therapy (ART) plus low dose IL-2 (1.2 million units/m2) subcutaneously daily for 56 days | Drug: HAART<br> <br> * Other names: ARM 1, ARM 2, ARM 3;|
| Experimental: ARM 2<br>Arm 2 (N=5) received ART plus a single infusion of approximately 5 to 11 billion CD4-zeta gene modified T cells. | Biological: T cells<br> <br> * Other names: ARM 2, ARM 3;|
| Experimental: ARM 3<br>Arm 3 (n=5) received ART plus IL-2 (1.2 million units/m2) and a single infusion of approximately 5 to 11 billion CD4-zeta gene modified T cells. | Drug: HAART<br> <br> * Other names: ARM 1, ARM 2, ARM 3;Biological: T cells<br> <br> * Other names: ARM 2, ARM 3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of CD4-zeta T cells with and without IL-2 in the setting of HAART | To assess and compare the safety of each arm when comparing related adverse events reported of subjects on study through the end of study (week 54). | Through study completion, an average of 1 year | 
| Effect of IL-2 on the Persistence of CD4-zeta T cells | Subjects who received IL-2 plus gene-modified cells versus those who received cells alone will have greater numbers gene-modified cells in both PBMCs and rectal lymphoid tissue. This will be done by quantifying residual virus in the reservoir using more modern techniques that permit quantification of small amounts of virus in the rectal lymphoid tissue and to quantify specifically replication competent HIV (versus total HIV). | Through study completion, an average of 1 year | 
| To compare the viral load of subjects from baseline to the end of study. | Determine the effect of CD4-zeta infusions with and without IL-2 on viral load (plasma HIV-1 RNA, tissue HIV-1 RNA, and frequency of latent replication-competent HIV-1 in PBMC) at study specific timepoints. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1