Trial Information

Autologous Stem Cell Rescue With CD133+ Selected Hematopoietic Progenitor Cells in Patients With High-Risk Neuroblastoma

Researchers want to learn if a CD133+ selected autologous stem cell transplant can help to
control the disease in patients with high-risk neuroblastoma. After your cells are
collected, they will be treated in the cell processing lab using the CliniMACS device. This
device will separate out the CD133+ cells. These selected cells will then be given back to
you on the day of transplant.

If you are found to be eligible to take part in this study, you will have a small plastic
tube placed in the collar bone area or the femoral vein (groin area). This is called a
central venous catheter (CVC). You will sign a separate consent form for the CVC placement
and the general anesthesia that is given. There may be several weeks between the collection
of stem cells and the reinfusion of these cells after high-dose chemotherapy. If the CVC is
placed in the femoral vein, the CVC will be removed after the stem cells are collected and a
new CVC will be placed in the collar bone before you are admitted for the stem cell
transplant. The CVC will be used for chemotherapy, fluids, blood products, stem cells, and
other medications. The CVC will remain until it is no longer needed (usually 2-3 months).

To help move the needed stem cells from your bone marrow to your blood, a drug called G-CSF
(filgrastim) will be injected under the skin. These injections may be given once a day for
Days 2-7. You or your caregiver will be taught how to give the injections at home. After 2
days of filgrastim injections, a blood sample (about 4 teaspoons each time) will be drawn
each day until you begin leukapheresis. This blood test is used to check the number of stem
cells and to watch for possible side effects. You will then be instructed to either
continue with the daily injections or stop. When the number of stem cells in the blood is
high enough, you will go to the MD Anderson Apheresis Unit to have your stem cells
collected.

The procedure to collect your stem cells is called leukapheresis. It is similar to donating
platelets to a blood bank. For this procedure, the stem cells will be removed from the
blood through the CVC, and the remaining blood will be given back to you through the CVC.
You will have one leukapheresis procedure per day, for 1-5 days in a row, until enough stem
cells are collected for the transplant. "Back-up" cells (extra cells collected during the
leukapheresis procedure) will also be collected. These cells will be stored in the cell
processing lab and may given back to you later if your white cell count does not recover.
Each leukapheresis procedure takes about 4-6 hours. This research study will use the
CliniMACS device to process the blood and separate the cells needed for transplantation.
Researchers will test a small sample of the collected cells to see if any tumor cells that
might be present in the blood before using the CliniMACS device are no longer present in the
processed blood after using the device.

Carboplatin and etoposide are designed to interfere with the growth of cancer cells by
stopping cell division, and melphalan is designed to damage the DNA (the genetic material)
of cells. The combination of carboplatin, etoposide, and melphalan causes a large amount of
bone marrow cells to die, which stops blood cells from being produced as normal. In order
to try to restart the production of blood cells, an autologous stem cell transplant is often
performed. For an autologous transplant, stem cells are removed from the blood. Usually
when stem cells are collected, they are either given back to the patient as collected, or
else a smaller group of cells that have a certain "marker" on their cell surface is selected
(separated out) before being given back to the patient. The CliniMACS device is a machine
that processes blood and separates the cells needed for transplantation. The CliniMACS
device is designed to select stem cells with a different marker on the cell surface than is
normally selected. The marker is called CD133+, and researchers believe that transplanting
cells that have this marker will make the infused cells less likely to be contaminated with
neuroblastoma cells, compared to the standard method of cell selection.

After 5 days of leukapheresis procedures, if the number of stem cells collected is lower
than a certain level, you will no longer be eligible to take part in the study.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. If these tests
have been performed recently, they may not need to be repeated. To check the status of the
disease, you will have CT scans, bone marrow aspirations and biopsies, and a chest x-ray.
The CT scans will be performed on the chest, abdomen, and pelvis (and if needed, the brain).
To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with
anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
You will have a pulmonary function test (to measure lung function), an echocardiogram (to
measure heart function), and an electrocardiogram (EKG -- a test to measure the electrical
activity of the heart). You will have a physical exam, including measurement of vital signs
(such as blood pressure and heart rate), height, and weight. Blood (about 4 tablespoons)
will be drawn for routine tests and to check for diseases such as hepatitis and HIV.
Females who are able to have children must have a negative urine pregnancy test. You will
also have a 12 or 24-hour urine test before carboplatin can be given. For this test, you
will collect your urine over 12 or 24 hours. You will be provided with a container to
collect the urine in. This test will be used to help decide the dosing of carboplatin that
you receive.

After enough stem cells are collected, and at a time decided upon by your neuro-oncologist
and transplantation doctors, you will be admitted to the hospital to receive fluids and then
the chemotherapy drugs carboplatin, etoposide, and melphalan, according to the standard
schedule. After the chemotherapy, you will have 3 "rest" days where no chemotherapy is
given.

On the day after the third rest day, your stem cells will be infused back into your CVC. To
help speed up the recovery of your white blood cells, a drug called filgrastim will be
injected under the skin. You will receive a filgrastim injection under the skin once a day,
until the white blood cell count recovers (usually 2-3 weeks). You may also receive
standard antibiotics, fluids, and/or other medications, if your doctor feels it is necessary
based on symptoms you may have. While you are in the hospital, you will have physical exams
once a day. Blood (about 4 teaspoons each time) will be drawn about 3-7 days per week,
until your blood counts are fully recovered and any side effects of the chemotherapy have
resolved. At that time, you will be able to leave the hospital.

From the time you leave the hospital until about Day 60, you will have follow-up visits at
least once per week. At these visits, you will have a physical exam. Blood (about 4
teaspoons each time) will be drawn for routine tests. However, your participation in this
study will not be over until after your annual follow-up at which time you will have a
medical history and physical exam, blood (about 4 teaspoons) drawn for routine tests, and a
CT scan.

If the disease gets worse or intolerable side effects occur at any time in this study, you
will be taken off study.

This is an investigational study. All of the drugs used in this study are commercially
available and FDA approved for use in neuroblastoma. The CliniMACS device is not
commercially available or FDA approved. It has been authorized for use in research only.

Up to 20 patients will take part in this study. All will be enrolled at M.D. Anderson.