Clinical Trials

Study : NANT 2001-02

Protocol Title: ¹³¹I-Metaiodobenzylguanidine (MIBG) with Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase II NANT Study (N2001-02)

Layman’s Title: ¹³¹I-MIBG + High Dose Chemotherapy and Stem Cell Transplant for High Risk Neuroblastoma

Study Chair: Gregory Yanik, MD. (University of Michigan)

What is this study about:

This study will combine three chemotherapy drugs in high doses (carboplatin, etoposide and melphalan) that have been used together in many patients with neuroblastoma with the experimental anti-cancer agent called Metaiodobenzylguanidine (MIBG) followed by stem cell rescue. MIBG is a substance that is absorbed (or "taken up") by neuroblastoma tumor cells. MIBG can be combined together with radioactive iodine (¹³¹I) in the laboratory to form the radioactive compound ¹³¹I-MIBG. The ¹³¹I-MIBG compound delivers radiation to the neuroblastoma cancer cells and causes them to die. Carboplatin, Etoposide and Melphalan (CEM) are chemotherapy drugs which all are known to have anti-cancer effects in neuroblastoma and other tumors.

Both ¹³¹ I-MIBG and CEM kill normal blood cells as a side effect. Blood cells include white blood cells, red blood cells and platelets - all of which are needed for you to live. All patients who choose to take part in this study will have their own stem cells collected and stored. Therapy with ¹³¹ I-MIBG + CEM will be followed by giving patients their own Stem Cells back (called an autologous stem cell transplant).. These stem cells can re-grow all the normal blood cells. The infusion of stem cells does NOT help in killing the tumor, but allows you to tolerate the higher doses of the anti-cancer drugs, ¹³¹ I-MIBG + CEM, that are being used to kill the tumor. This approach was tested in a previous phase I study in the NANT consortium that established the doses of MIBG that can be used together with CEM chemotherapy and stem cell transplant safely. This phase II study of MIBG and CEM chemotherapy + stem cell transplant will look at how many patients with neuroblastoma treated with this regimen will have a response (ie: disease gets smaller or goes away) and how long this response lasts.

Why is this study being done:

• How many patients with High-Risk Neuroblastoma will respond to ¹³¹I-MIBG + CEM by their tumors getting smaller or going away
• What effects - both good and bad - are seen in patients treated on this study.
• What amount of ¹³¹I-MIBG is taken up by the tumor, and if there is a relationship between this and how small the tumor gets after ¹³¹I-MIBG treatment.

Criteria that need to be met to participate in this study:

• Patients must be at least one year and no more than 30 years of age when registered on this study.
• Patients must have high risk neuroblastoma and either have tumor left after treatment started at diagnosis or have had the tumor grow back (relapsed) after getting some treatment
• Patients must an MIBG scan done and it must be positive for neuroblastoma.
• Patients must have a stem cell product available (either PBSC or bone marrow) that meets study criteria. If they don't already have stem cells frozen away then they must be able to have a stem cell harvest done to collect the necessary amount of stem cells for study entry and these stem cells must meet study criteria.
• Patients must have adequate heart, lung, liver, kidney and bone marrow function.

Patients cannot participate in this study if:

• They have had a stem cell transplant before.
• They have had treatment with ¹³¹I-MIBG before.
• They have been treated with at least a certain dose of Melphalan before.
• They have other medical problems that could get much worse if they had this treatment.
• They are on dialysis for badly working kidneys.
• They are pregnant or breast feeding.
• They have active infections such as hepatitis or fungal infections.
• They had total body radiation or radiation to the entire belly or a large amount of radiation to the liver or kidney (some radiation to the liver or kidneys is ok).
• They can't cooperate with the special precautions that are needed during MIBG treatment.

Study procedures:

Day –21	MIBG treatment. This is done at selected hospitals, you may need to travel to another city in another state to get MIBG
Day –21thru Day-16	Recovery from MIBG in the hospital. This takes several days until the radiation level from the MIBG is low enough that you can go home safely. (4-5 days)
Days -15	Travel home; Get ready to be admitted to the hospital for the transplant.
Day --8:	Admitted to the hospital to start transplant treatment
Day -7:	Carboplatin / Etoposide Melphalan (CEM)
Day -6:	Carboplatin / Etoposide Melphalan
Day =-5:	Carboplatin / Etoposide Melphalan
Day--4:	Carboplatin / Etoposide
Day -3:	REST
Day -2:	REST
Day -1:	REST
Day 0:	STEM CELL TRANSPLANT
Day +1 thru Day +42	Recovery from transplant, discharge home. Get local radiation to remaining areas of neuroblastoma seen in the on study tests.
Day +60	Disease evaluation

MIBG treatment is done at a hospital that is set up to take care of patients that are treated with radioactive substances. For this study, these hospitals are located in San Francisco, CA, Philadelphia, PA, Ann Arbor, MI and Cincinnati, OH. Patients who get MIBG are considered to be "hot' or radioactive and special precautions are taken to care for you during this time until the radiation has gone down to a level where these precautions are no longer needed. You are in your own room and the time family members can be in the room with you is limited at first but will increase every day as the radiation level goes down. MIBG is given by IV over 2 hours.

Two weeks after MIBG treatment you are admitted to the hospital for stem cell transplant. CEM chemotherapy is given over 4 days. Carboplatin and Etoposide are given continuously by IV for 4 days and Melphalan is given IV over 30 minutes on the first 3 days. The stem cells are given back to you 3 days after all the chemotherapy has finished. This is followed by G-CSF to stimulate the growth of white blood cells. G-CSF is usually given until the white blood cell count recovers. After CEM + stem cell transplant, you will be in the hospital until there are enough white blood cells present in the blood to fight infection and you have recovered form the other side effects of CEM chemotherapy to go home from the hospital. Following this you will have local radiation remaining to tumor sites.

If you would like to download or print a sample consent form for this clinical trial, please click here : N01-02 Sample Consent Form

If you would like to download or view a video consent for this clinical trial, please click here: N01-02 Video Consent

If you would like to download this page in Microsoft Word format, please click here: N2001-02

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