IRB Number:

2093-05

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

Neuroblastoma is a solid, cancerous tumor that shows up as a lump or mass in the belly or around the spinal cord in the chest, neck, or pelvis. The standard treatment for neuroblastoma consists of anti-cancer drugs (chemotherapy), surgery, and radiation therapy. Children with high-risk neuroblastoma often respond to standard treatment at first, but there is a high risk that the cancer will come back. This study is being done to try to raise the number of children with high-risk neuroblastoma who can avoid having the cancer come back.

Prior to taking part in this study patients would have already had chemotherapy, surgery, radiation therapy, and stem cell transplant treatment. Patients were helped by this treatment.
The reason for this companion study is to compare two different treatments aimed at keeping or improving their response to previous treatments. This study involves the use of an investigational biologic therapy, ch14.18, a monoclonal antibody. Monoclonal antibodies are proteins made in the laboratory, designed to bind to specific cancer cells. ch14.18 was designed to bind to neuroblastoma cells and other cancer cells that express the GD-2 antigen. When ch14.18 binds to the neuroblastoma cells, the body's immune system is excited to attack and kill the neuroblastoma cells. Ch14.18 represents a new kind of cancer therapy that, unlike chemotherapy and radiation, targets the death of cancer cells without killing nearby healthy cells. There is laboratory proof to suggest that ch14.18 can target the body's own immune cells to get rid of cancer cells. These immune cells armed by ch14.18 include cells that are activated by GM-CSF and cells turned on by aldesleukin (IL-2). Prior studies had shown the safest doses of ch14.18 and IL-2 to be given after stem cell transplant.

GM-CSF and IL-2 are drugs that are like a fluid made by the body in everybody. Usually the body makes small amounts of GM-CSF that helps it to produce normal infection fighting white blood cells. The body also makes small amounts of IL-2 that helps white blood cells fight infection. It is now possible to make GM-CSF and IL-2 outside of the body and give humans much higher doses than their own body makes. There is some proof that, in the laboratory and in animals, GM-CSF and IL-2 raises the anti-cancer effect of monoclonal antibodies like ch14.18. The research staff wish to see if aldesleukin (IL-2) can help improve the helpfulness of ch14.18 in humans.

Who is Eligible to Participate in the Study?

-Under 31 years old
-Diagnosed with high-risk neuroblastoma.

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Once patients are registered on this study, they will be put in one of two treatment groups (Regimen A or Regimen B) by chance as in the flip of a coin. This is done by a computer. Patients will have an equal chance of being placed in either treatment group.

The two treatment groups are the following:

Regimen A: Treatment with Isotretinoin (Accutane) alone. Isotretinoin is a drug closely related to vitamin A and has been shown to help stop the growing of remaining neuroblastoma cells. Regimen A is the standard treatment and is the treatment patients will get if they choose not to take part in this study and they complete the Maintenance phase of treatment.

Regimen B: Treatment with Isotretinoin (Accutane), ch14.18, IL-2, and GM-CSF. Regimen B is the investigational group of the study. It is important to keep in mind that ch14.18 is an investigational drug and it is impossible to tell if the patient will be helped from its use.

The treatment given on each regimen is described below. Depending on the treatment group that was chosen, patients will be treated on Regimen A or Regimen B, not both.

Regimen A: Isotretinoin

About two months following stem cell transplant, patients will begin a six-month treatment with isotretinoin. Patients will take this drug two times a day by mouth for 14 days and then not take it for the following 14 days. This 28-day course will be repeated six times.

Regimen B: Ch14.18, IL-2, GM-CSF, Isotretinoin
Treatment for courses 1, 3, and 5 with GM-CSF

GM-CSF will be given directly into a vein in the patient?s arm for two hours or as an injection under the skin daily from Day 0 through Day 13. Ch14.18 Monoclonal Antibody will be given directly into a vein in the patient's arm for five hours daily for four days (Days 3- 6). Isotretinoin will be given by mouth twice a day for 14 days (Days 10-23).

Treatment for courses 2 and 4 with Aldesleukin (IL-2)

IL-2 will be given by vein in the patient's arm for 24 hours a day for four days during the first week of each course (Days 0-3) and will then be given again the second week of each course (Days 7 -10). Ch14.18 Monoclonal Antibody will be given directly into a vein for five hours daily for four days (Days 7- 10). Isotretinoin will be given by mouth twice a day for 14 days (Days 14-27).

Treatment for course 6 with Isotretinoin only

Isotretinoin will be given by mouth twice a day for 14 days (Days 0-13).

Standard Medical Tests

Before treatment on this study begins, during and after treatment, patients will need to have a group of standard medical tests:

- Physical exam
- Blood tests
- Bone marrow exam
- Various scans (MIBG, CT, MRI, Bone Scan)
- Tests of kidney function
- Tests of lung and heart function
- Urine tests

How long will the Study run?

Patients will be in the study for about six months. The research staff would like to keep track of the patient's medical condition for ten years after they are done taking part in the study.

Sponsor(s): Children's Oncology Group (COG)

Study Activation/Registration Date: 11/21/2005

IRB Review and Approval Date: 10/28/2005

Study Type: Treatment

Projected Accrual: The plan is to have up to 423 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Vilmarie Rodriguez, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/07/2008