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

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

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).

Study Overview

• Status: Completed
• Conditions: HIV-1 Infections
• Intervention / Treatment: Drug: HAART; Biological: T cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM 1; 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; Other Names: ARM 1, ARM 2, ARM 3
Experimental: ARM 2; 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; Other Names: ARM 2, ARM 3
Experimental: ARM 3; 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; Other Names: ARM 1, ARM 2, ARM 3; Biological: T cells; Other Names: ARM 2, ARM 3

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Naomi Aronson, MD, Walter Reed Army Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: November 5, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: HIV-1
• Other Study ID Numbers: WU #8829-99

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO