Fourth Ventricle Infusions of Autologous Ex Vivo Expanded NK Cells in Children With Recurrent Posterior Fossa Tumors
Conditions
Brain Cancer
Conditions: official terms
Brain Neoplasms - Central Nervous System Neoplasms - Infratentorial Neoplasms
Conditions: Keywords
Brain Cancer, Brain tumor, Recurrent posterior fossa tumors, Central nervous system, CNS, Artificial antigen- presenting cells, aAPC, Natural killer cells, NK, Ommaya reservoir
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Natural Killer (NK) Cells
Type: Biological
Overall Status
Recruiting
Summary
The goal of this clinical research study is to learn if infusions of a particular type of patients' own white blood cells called natural killer (NK) cells can reliably and safely be given to patients with brain tumors after the cells have been through a procedure to expand (increase) their numbers.

Researchers also want to learn if NK cells infused through the ommaya reservoir can help to control the disease in patients with advanced brain tumors. The ommaya reservoir is a catheter system through which NK cells will be infused directly into an area of the brain called the fourth ventricle.

This is the first study of NK cells infused into the fourth ventricle of the brain in humans.
Detailed Description
Study Groups If you are found to be eligible to take part in this study, you will be assigned to a dose level of NK cells based on when you join this study. Up to 4 dose levels of NK cells will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of NK cells is found.

NK Cell Collection, Expansion, and Infusion:

Blood (up to 10 tablespoons) will be drawn through your central venous catheter if you have one, or through a needle stick.

Your NK cells will then be processed in The Cell Therapy Laboratory GMP facility at MD Anderson to make increased numbers of NK cells. Leftover blood from this process and/or extra NK cells beyond what is needed for the study will be used to study the appearance and function of your NK cells.

Your NK cells will be destroyed if you are found to not be eligible to receive the infusions or if you leave the study early.

If you do not already have an Ommaya catheter that has been placed in the fourth ventricle of your brain, you will have one placed before receiving the NK cells. You will sign a separate surgical consent form that will describe the procedure in more detail.

You will receive the NK cells 3 times a week (at least 1 day apart) for the first 3 weeks in each 4-week cycle. These infusions will be given to you over about 3 minutes through the ommaya reservoir catheter.

On the days of the NK cell infusions, you will take the following drugs to lower the risk of side effects:

- You will take Tylenol (acetaminophen) by mouth 1-2 hours before the infusion. If the doctor thinks it is needed, you will take it again 4-6 hours later.

- You will take Benadryl (diphenhydramine hydrochloride) before the infusion by mouth or by vein over about 30 minutes. If the doctor thinks it is needed, you will take it again 4-6 hours later.

Study Visits:

The screening tests may be repeated if your NK cell infusion is delayed more than 30 days.

If more than 4 weeks have passed since you had an MRI at screening, it will need to be repeated before receiving the NK cells in Cycle 1.

Before receiving the first NK cell infusion in Cycle 1, you will have a spinal tap to withdraw a small amount of CSF from around your spinal cord to check for tumor cells. If tumor cells are found, the procedure will need to be repeated within 7 days before receiving the NK cell infusion in Cycle 2. A spinal tap (also called a lumbar puncture) is when fluid surrounding the spinal cord is removed by inserting a needle into the lower back. The affected area is numbed with local anesthetic during the procedure. If tumor cells are not found, the procedure will be repeated after you receive the NK cells in Cycle 3.

Before receiving the first NK cell infusion in Cycles 1 and 3:

-You will have a physical exam.

Within 7 days before receiving the first NK cell infusion in Cycles 1-3, blood (about 1 tablespoon) will be drawn for routine tests.

On the days of the NK cell infusions in Cycles 1-3:

- You will have a physical exam.

- Right before the NK cell infusion, CSF will be withdrawn from the ommaya reservoir and used for routine tests. The CSF will also be used to study any tumor cells or NK cells in the CSF.

After you finish Cycle 1 and within 30 days after finishing Cycle 3, you will have an MRI of the brain to check the status of the disease. You will also have an MRI of the spine if the doctor thinks it is needed.

Length of NK Cell Dosing:

You may receive up to 3 cycles of the NK cells. You will no longer be able to receive the NK cells if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visit.

End-of-Dosing Visit:

Within 30 days after completing Cycle 3:

- You will have a physical exam.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will have an MRI of the brain and spine to check the status of the disease.

- You will have a spinal tap to withdraw a small amount of CSF from around your spinal cord to check for tumor cells.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 21 Years
Minimum Age: N/A
Gender: Both
Criteria: Inclusion Criteria:

1. Age: < 22 years at the time of recurrence or progression

2. Diagnosis: Patients with recurrent/refractory MB, AT/RT or ependymoma involving the brain and/or spine at original diagnosis or relapse will be eligible. They must have histological verification at diagnosis and/or relapse. Patient with these tumors who did not present at diagnosis in the PF but have relapsed in the PF will be eligible and those who initially presented in the posterior fossa but have now relapsed outside the PF will also be eligible.

3. Patient must have either measurable or evaluable tumor and an adequate CSF flow as assessed by: - MRI of the brain and spine (with and without gadolinium contrast), - MRI with CINE sequence of the brain and spine. - If CSF flow is visualized from the posterior aspect of the brainstem to the CSF spaces posterior to the cervical, thoracic, and lumbar spine, then the protocol will proceed. CSF flow in these studies will be judged to be absent or present (not quantified) by neuroradiologist. If CSF flow is not visualized, then a nuclear medicine CSF flow study may be performed.

4. Presence of, or agreement to have surgery to place, an implanted catheter in the fourth ventricle to receive NK cell infusion.

5. A minimum of 14 days between last dose of chemotherapy and study enrollment (NOTE: NK cells can be infused if 14 days have elapsed since the patient's last dose of chemotherapy).

6. A minimum of 14 days between last dose hematopoietic growth factor and study enrollment (NOTE: NK Cells can be infused if 14 days have elapsed since the patient's last dose of hematopoietic growth factor).

7. Life expectancy of at least 12 weeks in opinion of PI and/or designee.

8. Lansky score of 50 or greater if 16 years of age (NOTE: Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score).

9. Neurologic deficits must have been relatively stable for a minimum of 1 week prior to study enrollment.

10. Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy.

11. Patient must be 4 weeks off any palliative radiation or craniospinal radiation

12. Adequate bone marrow function defined by an ANC of >/= 1000/µL, platelet count of >/= 30,000 and hemoglobin of >/= 9.0 g/dl

13. Adequate liver function test with bilirubin
14. Patients with a seizure disorder may be enrolled if well-controlled and on non- enzyme inducing anticonvulsants

15. The NK cell donor must meet standard medical donor criteria for collection of peripheral blood cells.

16. Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent

Exclusion Criteria:

1. Enrolled in another treatment protocol

2. Evidence of untreated infection

3. Pregnant or lactating women
Location
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Status: Recruiting
Start Date
March 2015
Sponsors
M.D. Anderson Cancer Center
Source
M.D. Anderson Cancer Center
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page