Trial Information

CD19-specific T Cell Infusion in Patients With B-Lineage Lymphoid Malignancies After Autologous Hematopoietic Stem Cell Transplantation

Study Plan:

This study has 3 steps: chemotherapy, a stem cell transplant, and gene transfer.

The chemotherapy combination in this study (carmustine [BiCNU®], cytarabine
[Cytosar-U®], etoposide [Vepesid®], melphalan [Alkeran®], and rituximab [Rituxan®]) is given
to try to destroy any remaining tumor cells and prepare the body for the stem cell
transplant and T cell infusion.

A stem cell transplant is designed to help the body attack the cancer cells that may remain
after chemotherapy.

The gene transfer involves drawing blood, separating out T cells, changing the cells' DNA in
the laboratory, and returning the genetically changed cells back to the body. T cells are a
type of white blood cell that fight infection. The type of gene transfer being used in this
study is designed to help your T cells better fight B-cell lymphoma. These genetically
changed T cells are designed to fight B-cell lymphoma by targeting CD19 (a chemical "marker"
that is found on certain B-cell lymphoma cells).

IL-2 (Proleukin®) is designed to help T cells grow. In this study, researchers want to
learn if it can help the genetically changed T cells grow and last longer in the body.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of T cells, with or without IL-2, based on when you joined this study.

The first group of participants will receive the lowest dose of T cells. Each new group
will receive a higher dose of T cells than the group before it, if no intolerable side
effects were seen. Up to 4 dose combinations of T cells will be tested.

Tests Before Leukapheresis:

Before each of the 2 leukapheresis procedures (described below), the following tests and
procedures will be performed:

- Blood (about 4 tablespoons) will be drawn and used for routine tests and to look for
diseases such as hepatitis and HIV.

- A chest X-ray will be performed to check for infection.

- You will have an electrocardiogram (ECG -- a test that measures the electrical activity
of the heart).

Leukapheresis #1 or Standard Blood Draw (For Collecting T Cells):

You will visit the Apheresis Clinic at M. D. Anderson to have leukapheresis performed.
Leukapheresis is a procedure for removing blood from the body in order to collect specific
blood cells. The remaining blood is then returned to the body.

Blood will be drawn through a needle in a vein in one arm, then passed through a machine,
and then the remaining blood will be returned back to you through a needle in a vein in your
other arm. The machine will remove a sample of your white blood cells. This process will
take about 3 hours to complete.

Blood may also be collected through a standard blood draw. Blood (less than 7 tablespoons)
containing circulating T cells will be drawn over 1-2 days using one or more needle sticks
in your arm.

Your white blood cell sample will be sent to a lab at M. D. Anderson so the genetically
modified T cell product can be made. The modified T cells will be grown in the lab.

It will take about 7 weeks to modify and grow the necessary number of genetically modified T
cells. If researchers are unable to create a high enough dose of T cells for you in the
lab, you will be taken off study.

Placement of Central Venous Catheter:

Before the second leukapheresis, you will receive a central venous catheter. This is a
sterile flexible tube that will be placed into a large vein in your upper chest, while you
are under local anesthesia. The study investigator will explain this procedure to you in
more detail, and you will be required to sign a separate consent form for it.

When possible, all drugs that need to be given by vein will be given using the catheter.
You will also receive the T cell product through the catheter.

Leukapheresis #2 (For Collecting Stem Cells):

About a month after your first leukapheresis, you will return to have the procedure repeated
a second time. This time, the blood cells collected will be a sample of blood-forming stem
cells. The stem cells will be given back to you after your chemotherapy. If a high enough
number of stem cells cannot be collected, however, you will be taken off study.

A stem cell transplant is part of this study's treatment plan, but in some cases,
participants in this study will have their stem cells collected as part of another research
study or for routine care.

Chemotherapy and Stem Cell Transplant:

After your stem cells have been successfully collected, you will be admitted to the hospital
to receive chemotherapy. You will stay in the hospital for about 3-4 weeks.

- On Day 1, you will receive carmustine by vein over 1 hour.

- Every 12 hours on Days 2-5, you will receive cytarabine by vein over 1 hour and
etoposide by vein over 3 hours.

- On Day 6, you will receive melphalan by vein over 30 minutes.

- On Day 7, the stem cells that were collected earlier will be given back to you
("transplanted") by vein over 30-45 minutes. Day 7 is also called Day 0, since it is
the day of the transplant. The days after the transplant are called Days +1, +2, and
so on.

- On Days +1 and +8, you will receive rituximab by vein over 4-6 hours.

After the stem cell transplant, the study investigator will decide if you are still eligible
to receive the T cell infusion (and IL-2, if you are assigned to receive it). If you have
any infections or intolerable side effects, or if you are taking certain types of steroids
by mouth or injection, you will be taken off study. If you do not receive the T cell
infusions, you would not need to return for the follow-up described below.

T Cell Infusion (Gene Transfer):

You will receive the T cell infusion sometime between Day +2 through Day +7. (The exact day
will be as soon as you are eligible.) The T cell infusion will be given by vein over 15-30
minutes. The infusion will be divided into two parts at least 24 hours apart. The first
part of the infusion will be a much smaller part to ensure that you have no immediate side
effects. During the infusion, your vital signs will be checked.

Before the T cell infusion, you will receive drugs to lower your risk of allergic reaction
to the T cells. Acetaminophen (Tylenol®) will be given by mouth, and diphenhydramine
(Benadryl®) will be given by vein over a few minutes.

IL-2 Administration:

If you are in Group 2 or 4, IL-2 will be injected under the skin, once a day for up to 14
days. The first dose will be on the day of your T cell infusion.

Before each IL-2 injection, you will receive drugs to lower your risk of allergic reaction
to the IL-2. Acetaminophen will be given by mouth. Diphenhydramine will be given by mouth,
or by vein over a few minutes.

Study Tests:

Every day while you are in the hospital, blood (about 2 teaspoons) will be drawn for routine
tests.

On the day of the T-cell infusion, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of vital signs and weight.

- You will be asked about any side effects you may have had.

- Your medical history will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

Within 1 day, 3 days, 1 week, and 2 weeks after the T cell infusion, the following tests and
procedures will be performed:

- You will have a physical exam, including measurement of vital signs and weight.

- Your medical history will be recorded.

- Blood (about 2 teaspoons each time) will be drawn for research to look for the modified
T cells and to measure the number of B cells and other (non-modified) T cells. Like T
cells, B cells are part of your immune system.

Follow-Up:

At about 1, 3, 6, and 12 months after the stem cell transplant, you will return for
follow-up visits. At each visit, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of vital signs and weight.

- Your medical history will be recorded.

- Blood (about 1-2 tablespoons) will be drawn for routine tests and for research to look
for the modified T cells and to measure the number of B cells and other T cells. Part
of the blood sample at 12 months will be tested for HAMA.

- Other tests to check your health may also be performed if needed, such as CT scans,
PET/CT scans, and/or bone marrow aspirations and biopsies.

If the disease comes back or a side effect occurs during the 12 months after the stem cell
transplant, you may be asked to return for additional follow-up visits as needed.

Length of Study Participation:

If you have any infections or intolerable side effects, you will be taken off study early.

If you complete the study as planned, you will be off-study after your last follow-up visit.

Long-Term Follow-Up:

For safety reasons, the U.S. Food and Drug Administration (FDA) requires patients receiving
gene transfer to have long-term follow-up for at least 15 years after receiving the gene
transfer. You will be asked to sign a separate consent form for long-term follow up. That
study is known as Protocol 2006-0676, and the follow-up will begin 1 year after the gene
transfer study.

This is an investigational study. The chemotherapy and stem cell transplant in this study
are commercially available and FDA approved. The gene transfer is not commercially
available or FDA approved. At this time, gene transfer is only being used in research.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.