NANT 2017-01

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What is this Study About

The purpose of this study is to learn more about a new treatment combination for your neuroblastoma that uses a chemical agent called metaiodobenzylguanidine (MIBG) together with an intravenous (IV) drug called dinutuximab. MIBG is taken up by neuroblastoma tumor cells. MIBG can be combined with radioactive iodine (131I) in the laboratory to form the radioactive compound 131I-MIBG. 131I-MIBG delivers radiation to the neuroblastoma cancer cells and causes them to die. 131I-MIBG lowers the number of blood forming cells (called stem cells) in the bone marrow when it is given at higher doses as in this study. Because of this, all patients will get back their own stem cells to help the bone marrow recover from this therapy.

Dinutuximab works differently than most standard chemotherapy drugs. Dinutuximab is a monoclonal antibody. Monoclonal antibodies are proteins made in the lab, designed to attach to specific targets on cancer cells. When dinutuximab attaches to neuroblastoma cells, the body’s immune system is stimulated to attack and kill the neuroblastoma cells. Dinutuximab represents a new kind of cancer therapy called immunotherapy which, unlike chemotherapy and radiation, targets the cancer cells without destroying nearby healthy cells.

Laboratory studies have shown greater anti-cancer effects when radiation is given before an immunotherapy treatment. Some clinical responses have been seen in adults when radiation has been combined with different types of immunotherapy in treating their cancers.

Giving dinutuximab together with 131I-MIBG may help the 131I-MIBG kill more neuroblastoma cells. This is the first study to test giving dinutuximab together with 131I-MIBG. We want to find out if giving increasing doses of 131I-MIBG along with dinutuximab can be tolerated. We also want to see how effective this drug combination is against relapsed or refractory neuroblastoma.

Dinutuximab is a drug that has been approved by the Food and Drug Administration (FDA) for treating newly diagnosed patients with neuroblastoma. The use of dinutuximab in combination with 131I-MIBG for the treatment of relapsed or refractory neuroblastoma is considered experimental.

Why is this Study Being Done?

• To determine the highest safe dose of 131I-MIBG that can be given with dinutuximab to children with refractory or recurrent neuroblastoma without causing severe side effects

• To find out what side effects there are from giving 131I-MIBG and dinutuximab together on this schedule at different dose levels

Other Things We are Trying to Learn During this Study

• To see if your tumor gets smaller after treatment with 131I-MIBG and dinutuximab

• To learn what happens to your immune system and other proteins in you when giving different doses of 131I-MIBG with dinutuximab

• To see what effect giving different doses of 131I-MIBG has on your body in making an antibody to the Dinutuximab

• To see what effect treatment with 131I-MIBG in combination with dinutuximab has on the cells of your immune system that surround and invade your tumor

• To describe the amount of neuroblastoma tumor found in the blood and bone marrow by testing samples with a new test (called NB5 assay)

Criteria That Needs to be Met to Participate in this Study

• Patients must be at least 1 year old and younger than 30 years of age

• Patients must have evidence of 131I-MIBG uptake in at least one site of tumor (in either bone or soft tissue)

• Patients must have high risk neuroblastoma and have a response to prior therapy that fits into at least one of the following categories:

  • Relapsed or progressive disease at any time before study enrollment.

  • Refractory disease: patients had “no response” and still have persistent sites of disease after receiving a minimum of 4 cycles of induction treatment and have never had a disease relapse or progression.

  • Persistent disease: partial response with disease present after standard therapy and no disease relapse or progression *some patients may need a surgical biopsy of the tumor for enrollment

• Patients must have adequate heart, kidney, liver, lung, pancreas, neuropsychological and bone marrow functions. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study

• Patients must have fully recovered from all prior chemotherapy, immunotherapy, or radiotherapy

• Patients of childbearing potential must have a negative pregnancy test and agree to effective contraceptive

Criteria that Would Make Patients Ineligible to Participate in this Study

• Total lifetime dose of 131I-MIBG no more than 20 mCi/kg

• Patients who are breast feeding

• Patients and/or families who, in the opinion of the investigator, may not be able to comply with the safety monitoring/radiation isolation requirements of the study

• Patients with disease of any major organ system that would make it difficult to withstand therapy

• Patients who have received prior allogeneic stem cell transplant, solid organ transplantation or prior total body irradiation

• Patients who have a known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. (testing of patients not known to be infected with these viruses is not required prior to study registration).

• Patients with a history of having to discontinue anti-GD2 antibody therapy due to toxicity are not eligible

• Patients with prior anti-GD2 therapy given in combination with therapeutic 131I-MIBG

• Patient’s maximum total allowable dose of 131I-MIBG, that can be given per institutional guidelines, is not at least 90% of the calculated 131I-MIBG dose

• Patient who declines participation in NANT 2004-05, the NANT Biology Study

Study Schedule / Treatment

This study will test up to 3 combination doses of dinutuximab and 131I-MIBG in groups of 3-6 patients. Dose levels will be assigned upon enrollment. Each treatment course is 57 days and patients may receive up to two courses of therapy as long as all protocol-defined criteria are met prior to the start of the second course. This diagram below outlines one course of the therapy on this study.

Patients will have their neuroblastoma evaluated by bone marrow tests and scans between days 43-57 of courses 1 and 2.

Patients with stable disease or who are having clinical benefit from dinutuximab and 131 I-MIBG combination therapies may continue receiving protocol therapy provided that the patient meets criteria for starting subsequent course and does not meet any criteria for removal from protocol therapy or off-study criteria.

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