Redirected High Affinity Gag‐Specific Autologous T Cells for HIV Gene Therapy - Full Text View

Sponsor:	University of Pennsylvania
Information provided by:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00991224

Purpose

This research study is being carried out to study a new way to possibly treat HIV. T‐cells are one of the white blood cells used by the body to fight HIV. CD8 T‐cells are a type of T‐cell used by the body to detect and kill cells which have been infected by foreign viruses or organisms,including the HIV virus. CD8 T‐cells must identify the HIV virus in order to kill it. Because HIV is constantly changing the way it looks to the CD8 T‐cells, some of the HIV virus escapes detection and is not killed by the CD8 T‐cells.

This research study uses a T cell receptor (TCR) protein specific for HIV (SL9 TCR) and adds it to the CD8 T‐cells in the laboratory in order to help the CD8 T‐cells recognize the constantly changing HIV virus and make it able to fight HIV more efficiently. TCR stands for T cell receptor TCRs are found on the surface of T cells and allow the T cells to recognize other cells. Laboratory studies have shown that when CD8 T‐cells are modified with SL9 TCRs, they kill cells that are infected with HIV better than normal CD8 T‐cells can. On the basis of these laboratory results, there is the potential that SL9 TCRs may work in people infected with HIV and improve their immune system by killing HIV infected cells and thus may help control HIV infection.

Two different SL9 TCRs will be tested in this study, WT‐gag‐TCR and α/6‐gag‐TCR. Two different types of SL9 TCRs are being used in this research study because the laboratory studies suggest that the different SL9 TCRs will function differently depending on the amount of virus in your body. A goal of this clinical study is to test the effects of infusions of either SL9 TCR in the presence or absence of a viral load.

Condition	Intervention	Phase
HIV Infections	Biological: WT-gag-TCR modified T cells Biological: α/6-gag-TCR modified T cells Other: STI or Drug Holiday	Phase I

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Factorial Assignment, Safety/Efficacy Study
Official Title:	A Pilot, Open Label, Multi Arm, Single Ctr Study to Evaluate Safety & Tolerability of Escalating Doses of Autologous T Cells Modified With Lentiviral Vectors Expressing High Affinity Gag-specific TCRS in HLA-A02 Patients With HIV

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: AIDS

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

To determine optimal dose and to evaluate the safety and tolerability of the study drug. [ Time Frame: 3 years from end of study ] [ Designated as safety issue: Yes ]
To monitor for delayed adverse events associated with lentiviral vector gene transfer (RCL and insertional oncogenesis) [ Time Frame: 3 years from end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the antiviral effects of WT‐gag‐and α/6‐gag‐ TCR transduced cells in patients with low and high antigen load (presence and absence of viremia) [ Time Frame: 3 years from end of study ] [ Designated as safety issue: Yes ]
To monitor engraftment of vector modified cells in the peripheral circulation [ Time Frame: 3 years from end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	48
Study Start Date:	November 2009
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm 1: Experimental Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 at the time of enrollment, a CD4 nadir >200 and a recorded historical viral load setpoint, will receive a WT-gag-TCR modified autologous T cells, followed one week later by a 16 week treatment interruption.	Biological: WT-gag-TCR modified T cells Single dose of WT-gag-TCR modified T cells infused over 3 consecutive days. Other: STI or Drug Holiday Subjects will stop taking antiviral medications for 16 weeks.
Arm 2: Experimental Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 at the time of enrollment, a CD4 nadir >200 and a recorded historical viral load setpoint, will receive a α/6-gag-TCR modified autologous T cells, followed one week later by a 16 week treatment interruption.	Biological: α/6-gag-TCR modified T cells Single dose of WT-gag-TCR modified T cells infused over 3 consecutive days. Other: STI or Drug Holiday Subjects will stop taking antiviral medications for 16 weeks.
Arm 3: Experimental Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 and a CD4 nadir >200. Subject will undergo an 16 week treatment interruption during which a single infusion of WT-gag-TCR modified autologous T cells at 8 weeks post STI.	Biological: WT-gag-TCR modified T cells Single dose of WT-gag-TCR modified T cells infused over 3 consecutive days. Other: STI or Drug Holiday Subjects will stop taking antiviral medications for 16 weeks.
Arm 4: Experimental Subjects who are HIV positive, taking medication to control virus, have an undetectable viral load, CD4 count greater than 450 and a CD4 nadir of >200. Subject will undergo an 16 week treatment interruption during which a single infusion of α/6-gag-TCR modified autologous T cells at 8 weeks post STI.	Biological: α/6-gag-TCR modified T cells Single dose of WT-gag-TCR modified T cells infused over 3 consecutive days. Other: STI or Drug Holiday Subjects will stop taking antiviral medications for 16 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18 years or older
Karnofsky Performance of 80 or higher
HLA-A2 Positive
Chronic HIV-1 infection
On stable HAART regimen (with no changes within 4 weeks of study entry)
Willing to undergo a limited treatment interruption of antiretroviral medication
CD4+ T cell count ≥450 cells/mm3
Documented CD4 nadir of ≥200 cells/mm3
Undetectable HIV-1 RNA
ARMS 1 and 2 only, at least a singe documented historic viral load set point reading
Lab Values: Hgb≥10 males; ≥9.5 females ; ANC≥1000/mm3 ; Platelets≥1000,000/mm3 ; Creatinine≤1.5 mg/dL ; AST, ALT ≤ 2.5xULN

Exclusion Criteria:

Current or prior AIDS diagnosis
Previous participation in any gene therapy using an integrating vector (subjects treated with Placebo will not be excluded)
History of cancer or malignancy (allowed to have successfully treated basal cell or squamous cell carcinoma of the skin)
Have history or current exam indicative of active or unstable cardiac disease or hemodynamic instability
Have history or current exam indicative of bleeding diathesis
Previous treatment with any HIV experimental vaccine within 6 months prior to screening
Use of chronic corticosteroids, hydroxyurea or immunomodulating agents such as IL2, interferon alpha, interferon gamma, granulocyte colony stimulating factors within 30 days prior to study entry (inhaled steroids are not exclusionary)
Currently breast feeding, pregnant or unwilling to use acceptable methods of birth control
Use of aspirin, dipyridamole, warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis
Active drug or alcohol use/dependence
Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
Receipt of a vaccination within 30 days prior to study entry
Have a known allergy or hypersensitivity to human serum albumin, DMSO or Dextran 40

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00991224

Contacts

Contact: Larisa Zifchak, BSN	215-349-8091	larisa.zifchak@uphs.upenn.edu
Contact: Joseph Quinn, BSN	215-349-8091	joseph.quinn@uphs.upenn.edu

Locations

United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Pablo Tebas, MD

Sponsors and Collaborators

University of Pennsylvania

More Information

Additional Information:

UPenn AIDS Clinical Trials Unit (ACTU) Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Pennsylvania ( Carl H. June, MD ; Director, Translational Research Programs, Abramson Cancer Center, Professor of Pathology and Laboratory Medicine )
Study ID Numbers:	810108
Study First Received:	October 6, 2009
Last Updated:	December 1, 2009
ClinicalTrials.gov Identifier:	NCT00991224 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:

HIV
HIV therapeutic vaccine

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on February 08, 2010