Evaluation of Recovery From Drug-Induced Lymphopenia Using Cytomegalovirus-specific T-cell Adoptive Transfer

Summary

The purpose of this research study is to learn if your own immune cells can be activated and multiplied in order to help your body fight off the tumor cells in your brain. The safety of this procedure will also be studied. This procedure, called CMV-autologous lymphocyte transfer or CMV-ALT is investigational which means that it is not approved by the US Food and Drug Administration (FDA) and is still being tested in research studies. Autologous lymphocyte transfer or ALT means that you will receive your own immune cells back (and not from another donor) as a treatment after they have been activated and grown to large numbers in a clinical lab.

It is believed that the body's immune (protection) system can attack tumor cells and kill them. Immune cells called T-lymphocytes (T-cells) can recognize special proteins on the surface of tumors as a signal to attack and fight the cancer. In most patients with advanced cancer, the immune system does not adequately destroy the tumor because the white blood cells or T-cells are not stimulated enough.

Before your T-cells can become active against tumor cells, they require strong stimulation. There are special "stimulator" cells in the body called Dendritic Cells (DCs) that can take up proteins released from cancer cells and present pieces of these proteins to T lymphocytes to create this strong stimulation. Dendritic cells taken from your blood will be "pulsed" or loaded with genetic material called RNA (ribonucleic acid), which stimulates the DC to change the RNA into a protein called pp65. This protein is produced by a common virus called Cytomegalovirus (CMV) that 70-80% of us have been exposed to in our lifetime. Recently, we have found that this virus is present in many malignant brain tumors. Brain tumors are very aggressive and, for reasons we do not yet understand, are difficult for the body to attack. The CMV virus is a target in the tumor that, if attacked by your immune systems cells, may prevent your tumor from growing. We have found that we can grow immune cells to very large numbers from the blood of people who have evidence of prior exposure to this virus. You will therefore be tested to determine if you have pre-existing antibodies to this virus in order to participate in this study.

We will use your DCs to activate and grow immune cells from your blood to large numbers in a clinical laboratory. These CMV-specific immune cells, called CMV-ALT, will be returned to your body when they have become activated. It is hoped that these cells will seek out and kill tumor cells that express the CMV viral protein and not attack normal cells. The transfer of immune cells that stimulates your immune system is called adoptive immunotherapy. We will evaluate two doses of immune cells in this study (Dose 1 and Dose 2). Depending on when you are enrolled in this study you will receive either Dose 1 or 2. The first six patients enrolled on this study will receive Dose 1 (the lower dose) and the next six patients will receive Dose 2 (the higher dose). We do not know at this time if either dose is more effective or safer to administer which is why we are testing both doses. Dose 2 will be a larger number of immune cells if the treatment is found to be safe in the first six patients treated during this study.

In this study we will also see, in some randomly selected patients, if giving an injection of the DC pulsed with pp65 RNA into the skin improves the function of the CMV-ALT treatment or not. You will receive three injections under the skin of either some of the same DC that were used to stimulate your immune cells in the clinical laboratory or three injections of saline (salt solution) under the skin starting with the infusion of the CMV-ALT. It is unknown if a DC injection will be beneficial to the immune cells or not so the responses will be compared in patients who receive DC versus saline injection with their CMV-ALT. After these three injections, blood will be collected to compare the responses between patients that received saline to those that received DC injections.

Conditions

• Glioblastoma

Interventions

BIOLOGICAL

CMV-ALT + CMV-DCs

CMV-ALT (3 X 10e7) with CMV-DCs (2 X 10e7)

BIOLOGICAL

CMV-ALT + Saline

CMV-ALT (3 X 10e7) with Saline

Sponsors & Collaborators

• John Sampson

  lead OTHER

Principal Investigators

• Gordana Vlahovic, MD · Duke University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-09-30

Primary Completion

2013-12-31

Completion

2015-04-30

Countries

• United States

Study Locations