Study of Intraventricular Infusions of Autologous ex Vivo-expanded NK Cells in Children With Recurrent/Refractory Malignant Posterior Fossa Tumors of the Central Nervous System. NOAH's (New Opportunity, Advancing Hope) Protocol

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 the cells show some form of abnormal cell growth during
the process and are unsafe for infusion, 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 lateral or 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 1 time a week (at least 3 days 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 before the infusion. 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 Cycles 1, 2, 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 before the infusion, which may be done at bedside.

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.

- You will have an MRI of the brain within 72 hours before the first NK cell infusion in
Cycle 1. An MRI of the spine will be performed at the same time if the doctor thinks it is
needed. If these scans show the disease has gotten worse since the time of screening, it will
serve as the baseline scan. You will still move forward with NK cell infusions if the doctor
thinks you are stable to receive infusions.

After you finish Cycle 3 and within 7 days after the last dose of NK cells, 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. MRIs can be performed earlier if the doctor thinks it is
needed.

You will have a brain MRI with a CINE study (checking the proper flow of CSF that surrounds
and flows in the brain and spine) to check the flow of CSF into the spine from the brain
before the first infusion of NK cells. This has to be performed any time after the placement
of the catheter and the first infusion of the NK cells.

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.

- Within 7 days after the last infusion of NK cells, 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 if your doctor thinks it is appropriate.

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. They must have histological
verification at diagnosis and/or relapse. Patient must have presented with these
tumors in the posterior fossa (PF) or relapsed in the PF.

3. Patient must have either measurable or evaluable tumor.

4. Presence of or determined by neurosurgery to be a candidate for an implanted catheter
in the ventricles to receive NK cell infusion.

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

6. Lansky score of 50 or greater if 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).

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

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

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

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

11. Patients with a seizure disorder may be enrolled if well-controlled and on non- enzyme
inducing anticonvulsants

12. 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. Extra-cranial metastasis

4. Chronic corticosteroid dependence (except replacement therapy)

5. Extensive disease, disease location, and/or co-morbid condition that the PI or
designee considers unsafe for surgical intervention of NK cell infusion

6. Pregnant or lactating women