NANT 2013-01

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What is this Study About

The purpose of this study is to learn more about a new treatment for your neuroblastoma that uses the body’s own natural defense (immune) system to kill neuroblastoma cells.  One type of immune cell is the natural killer (NK) cell. NK cells have the ability to kill tumor cells like neuroblastoma, but are only present in the body in small numbers.  This study uses an experimental process to grow (or “expand”) large numbers of NK cells in a laboratory from your own blood sample.  The expanded NK cell product can then be infused back into your body for treatment.

The first part of this study will involve treatment with expanded NK cells and dinutuximab.  Some experiments have shown that the combination of NK cells and another drug called dinutuximab worked better than either of these alone.  Dinutuximab is a monoclonal antibody, or protein made in the lab that can attach to targets on neuroblastoma cells to stimulate NK cells to attack them. Dinutuximab has been approved by the U.S. Food and Drug Administration (FDA) for use in the treatment of high risk neuroblastoma.

Once the combination of NK cells and dinutuximab has been shown to be safe, the second part of the study will open, and patients enrolled to this part of the study will receive NK cells with dinutuximab and another drug called lenalidomide.  Laboratory experiments have shown that the combination of NK cells, dinutuximab and lenalidomide may work better than NK cells and dinutuximab alone to kill neuroblastoma cells. Lenalidomide has been approved by the U.S. Food and Drug Administration (FDA) for use in the treatment of other types of cancer.

Why is this Study Being Done?

• To determine whether natural killer (NK) cells collected from patients can be successfully grown in the laboratory, shipped (fresh or frozen) and infused safely back into the patient.

• To determine the highest dose of NK cells that can be safely given with dinutuximab and lenalidomide without causing severe side effects.

• To learn about the side effects of NK cells given at different dose levels with dinutuximab with or without lenalidomide.

Other Things We are Trying to Learn During this Study

• To see how your tumor and immune system respond to this combination treatment, and to identify certain genes that may make it more or less likely that your tumor responds.

• To see how long expanded NK cells last in your body after infusing them, and to look at the levels of dinutuximab and special immune system markers in your blood throughout the study.

• To see if there are differences between the NK cells from neuroblastoma patients and NK cells from individuals who are not diagnosed with neuroblastoma.

• To determine the amount of neuroblastoma tumor in blood and bone marrow using the new test (called NB-5) and compare to the results of standard tests.

Criteria That Needs to be Met to Participate in this Study

• Patients must be 30 years of age or younger

• Patients must have high risk neuroblastoma with either refractory or relapsed disease. Some patients may require a biopsy prior to enrollment.

• Patients must have adequate heart, kidney, liver, lung and bone marrow functions.

• Patients enrolling onto the dose level (4) treated with NK Cells, dinutuximab and lenalidomide must be able to swallow whole capsules.

Criteria that Would Make Patients Ineligible to Participate in this Study

• Patients with a history of having to discontinue dinutuximab therapy due to toxicity must receive approval for enrollment

• Patients with known active CNS disease (excluding skull disease with intracranial extension).

• For enrollment on the dose level (4) treated with NK cells, dinutuximab and lenalidomide: patients with a hypersensitivity to the drug thalidomide or similar drugs.

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

• Patients who decline participation in NANT 2004-05, the NANT Biology Study.

Study Schedule 

This first part of this study will test up to 3 dose levels of expanded NK cells in groups of 3 to 6 patients. The dose level of NK cells will be assigned upon enrollment and all patients will receive NK cells (at their assigned dose level) in combination with dinutuximab at the standard dose used for patients with neuroblastoma.  In the second part of the study, patients will be enrolled on a fourth dose level to receive NK cells (at the dose level found to be safe across the first 3 groups) with both dinutuximab and lenalidomide at the standard doses used for patients with neuroblastoma. 

Treatment

The growth of the expanded NK cell product requires a single blood specimen collected 2-3 weeks prior to the start of treatment.

Each treatment course is 28 days and patients may receive up to twelve courses of therapy depending on the number of NK cells grown from the initial blood collection, and as long as all protocol-defined criteria are met prior to the start of each subsequent course.

The treatment course for the groups given only NK cells and dinutuximab is as follows (NOTE: This diagram outlines one course of the therapy on this study):

The treatment course for the group given NK cells, dinutuximab and lenalidomide is as follows (NOTE: This diagram outlines one course of the therapy on this study): 

*Negative study days are days prior to Study Day 1 (start of Dinutuximab).

Patients will have their neuroblastoma evaluated by bone marrow tests and scans within week 4 of courses 2, 4, 6, 9 and 12. Patients with stable disease or who are having clinical benefit from therapy 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.