GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma

Description

In this study the first step is to collect blood from the patient to make the GINAKIT cells. Once the GINAKIT cells are made they will be administered to the patient.

Patients will be treated on a single fixed dose level with Etanercept from now on. If there is severe toxicity related to the combination of GINAKIT cells and Etanercept, we will treat patients on lower dose level. Thus maximum 36 patients will be recruited on the on the combination therapy, including 18 patients potentially at the lower dose level. If we are not able to generate sufficient GINAKIT cells on the fixed dose level, we will treat you with the highest dose level that is achieved.

Before getting the GINAKIT cells, the patient will receive cyclophosphamide and fludarabine intravenously (through a needle inserted into a vein or a port-a-cath) for 2 days and then fludarabine alone for one more day. The patient will then receive ETANercept subcutaneously (through a needle just under the skin) once per week starting the day after chemotherapy for 5 doses. The patient will receive the GINAKIT cells the day after first dose of ETANercept.

The patient will be given an injection of GINAKIT cells into the vein through an IV line at the assigned dose. Before the patient receives the injection, they may be given a dose of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The injection will take up to 10 minutes. The patient will be monitored in the clinic after the injection for about 4 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children’s Hospital.

The patient will need to stay in Houston for 4 weeks after the infusion so investigators can monitor the patient for side effects. The patient will have follow-up visits (at weeks 1, 2, 3, 4 and 8; months 3, 6, 9, and 12; twice a year for 4 years and then once a year for the next 10 years – for a total of 15 years) and scheduled disease evaluations after the GINAKIT cell infusion (at week 6 and then as clinically needed).

If after 4 weeks the patient’s condition does not get worse, the patient may receive another round of lymphodepleting chemotherapy and infusion of GINAKIT2 cells. Reinfusion of cells may occur up to three times and the patient will have to meet treatment eligibility criteria at each lymphodepletion start. The patient will also receive ETANercept with the schedule at each time of treatment. Treatment eligibility are characteristics that must be met such as current health status and other items that ensure patients who could be made worse by participating in the study are not exposed to that risk. The eligibility also ensures researchers achieve accurate results

Before being treated, the patient will receive a series of standard medical tests as follows:

* Physical exam
* Blood tests to measure blood cells, kidney and liver function
* Blood tests to ensure the patient do not have tuberculosis.
* Buccal swabs (cheek scraping)
* Measurements of the patient’s tumor by routine imaging studies and bone marrow evaluation within 4 weeks (preferably 2 weeks) before start of lymphodepletion (no other cancer treatment should be given after these studies and the GINAKIT cell infusion). Imaging studies that have been used in the past to best assess the patient’s tumor will be used (Computer Tomogram (CT) or Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET/CT), and/or MIBG scan). A PET scan is an imaging test that uses radioactive material to look for disease in the body. A MIBG scan is an imaging test that uses radioactive material and a special scanner to find or confirm the presence of neuroblastoma.
* A urine pregnancy test. If that patient is pregnant both the patient and their parents will be informed of the pregnancy.

The patient will receive standard medical tests when they are getting the infusions and afterwards as follows:

* Physical exams
* Blood tests to measure blood cells counts, kidney and liver function.
* Subcutaneous injection of ETANercept.
* Measurements of the patient’s tumor by routine imaging studies 4-6 weeks after the infusion.
* Tumor biopsy at 2 weeks and between 4-6 weeks after the infusion and as clinically indicated thereafter. The evaluation at week 2 after the infusion is for research only and is done to see whether or not there are GINAKIT cells in the tumor. For all clinically indicated tumor biopsies a portion of the sample for research will be requested.
* If a tumor was in the bone marrow at the time of treatment, the procedure will be repeated at 2 weeks and between 4-6 weeks after the infusion and as clinically indicated thereafter. The evaluation at week 2 after the infusion is for research only and is done to see whether or not there are GINAKIT cells in the bone marrow. For all clinically indicated bone marrow collections a portion of the sample for research will be requested.

To learn more about the way the GINAKIT cells are working and how long they last in the body, an extra amount of blood will be obtained before the chemotherapy, on the day of the GINAKIT cell infusion (before and at the end of the infusion), 1, 2, 3, 4 and 8 weeks after the GINAKIT cell infusion, every 3 months for the 1st year, every 6 months for the next 4 years and then once a year for the next 10 years (for a total of 15 years). The amount of blood taken will be based on the patient’s weight with up to a maximum of 60 ml (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 ml (less than 1 teaspoon) per 1 kg of body weight on any given day. This volume is considered safe, but may be decreased if the patient is anemic (have a low red blood cell count). This blood will also be used to monitor the patient’s white blood cell levels. In the event the patient’s white blood cell counts are high, they will be admitted to the hospital where they will be treated with hydration, steroids or chemotherapy. The study doctor will discuss with the patient the best treatment options.

During the time points listed above, if the GINAKIT cells are found in the patient’s blood at a certain amount, an extra 5ml of blood may need to be collected for additional testing.

If the patient has a procedure where tumor samples are obtained, investigators will request a sample to be used for research purposes.

If the patient develops a second abnormal growth, significant blood or nervous system disorder during the trial, a biopsy sample of the tissue will be tested (if a sample can be obtained).

The patient will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as appropriate.

Because the patient will receive cells with a new gene in them they will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.