Ex-Vivo Expanded Allogeneic NK Cells For The Treatment Of Pediatric Solid Tumors

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 2 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. A second group will receive a higher dose,
if no intolerable side effects were seen.

After the recommended dose is found, an additional 14 participants may be enrolled in an
"Expansion Phase" and receive that dose of NK cells.

All participants will receive the same dose level of standard chemotherapy.

Study Drug Administration:

You will receive cyclophosphamide by vein over about 30 minutes on Days 1-5. You will also
receive etoposide by vein over about 60 minutes on Days 1-5. You will then rest (not receive
anything) on Days 6 and 7. You will then receive the NK cells by vein. The nurse and study
doctor will determine the length of the infusion based on volume that they get from the lab.
It should take no more than 1 hour.

You will be admitted to the hospital within 24 hours before you begin receiving chemotherapy
to receive it as an inpatient. You will stay in the hospital for all the chemotherapy and not
be discharged until after you have received the NK cell infusion and the doctor thinks that
it is safe for you to go home.

You will also receive mesna to help prevent side effects to the bladder. Mesna is given by
vein over a short amount of time at 3 different time points. When and how long you receive it
will depend on what the study doctor thinks is in your best interest. This will be discussed
with you.

You will be given standard drugs and fluids to help decrease the risk of side effects. You
may ask the study staff for information about how the drugs are given and their risks.

Length of Study:

You will receive the NK cells 1 time. You will then have study visits until 30 days after you
receive the NK cells. You will be taken off study if the disease gets worse, if intolerable
side effects occur, or if you are unable to follow study directions.

Study Visits:

Within 72 hours before you begin receiving chemotherapy:

- You will have a physical exam.

- Blood (about 3-4 tablespoons) will be drawn for routine tests, to check for the presence
of donor cells in your blood, and research tests to check the effects of the NK cells.
Some of these tests are being done before you receive the donor cells to compare to
samples that are taken after you receive them.

- Urine will be collected for routine tests.

Urine will be collected for routine tests every time you urinate while you are in the
hospital receiving chemotherapy.

Blood (about 2-3 teaspoons) will be drawn for routine tests 2 times each week from the time
you started chemotherapy until your blood cell counts recover from chemotherapy. This may
continue to be done after you leave the hospital.

Within 24 hours before you receive the NK cells, 3-4 days after you receive the NK cells, and
then every week until 30 days after you receive the NK cells and then at Months 3, 6, and 12:

- You will have a physical exam.

- Blood (about 2-4 tablespoons) will be drawn for routine tests, to check for the presence
of donor cells in your blood, and research tests to check the effects of the NK cells.
The research blood draws will continue only until Day 38.

- Depending on the type of disease that you have, blood (about 1 teaspoon) may be drawn
for tumor marker testing.

At the last of these visits, you will have MRI and/or CT scans to check the status of the
disease around 4 weeks after infusion. If the doctor thinks it is needed, this will be
repeated at 8 weeks after your NK cell infusion to check for pseudoprogression.
Pseudoprogression is when the tumor may appear to be getting worse soon after cell infusion
because the body is mounting an immune response to the tumor. But really either the tumor is
stable (has not changed) or is getting better. Depending on the type of disease that you
have, you may need to have additional studies that include MIBG, FDG-PET, bone marrow
aspiration and biopsy, tumor marker, and tissue biopsy at these visits to check the status of
the disease.

After the last visit, you will continue to be followed by your regular cancer doctor per the
standard of care. Information about how you are doing and the disease will be shared with the
study doctor for 1 year after the infusion of NK cells. Follow-up may continue after that if
you have any ongoing complications or side effects related to the infusion.

Inclusion Criteria:

1. Screening inclusion criteria: Patient age between 12 months and 40 years, inclusive at
the time of study entry.

2. Screening inclusion criteria: Patients with relapsed or refractory solid tumors and
without known curative therapy or therapy proven to proven to prolong survival with
acceptable quality of life.

3. Screening inclusion criteria: Patients older than 21 years must have a solid tumor
considered by study doctor to be of the childhood cancer type.

4. Screening inclusion criteria: Performance level as measured by Karnofsky >/=60% for
patients > 16 years of age or Lansky >/= 60% for patients
5. Screening inclusion criteria: Documentation of measurable or evaluable non-measurable
disease.

6. Screening inclusion criteria: At least one documented histological verification of
solid tumor diagnosis. Can be from original diagnosis or more recent.

7. Enrollment inclusion criteria: Patient must have fully recovered (i.e. returned to
baseline) from the clinically significant acute treatment-related toxicities of all
prior treatments prior to beginning treatment on this protocol with exceptions of
cytopenias resulting from persistent disease, hearing loss and alopecia.

8. Enrollment inclusion criteria: Performance level as measured by Karnofsky >/= 60% for
patients > 16 years of age or Lansky >/= 60% for patients
9. Enrollment inclusion criteria: Adequate renal function defined as: Creatinine
clearance >/= 60 mL/min/1.73m2 (calculated by 24h urine collection or nuclear GFR scan
if 24h collection is not possible) or a serum creatinine based on age and gender as
follows: Age 1 month to < 6 months, Maximum Serum Creatinine (mg/dL) Male 0.4, Female
0.4; 6 months to < 1 year, 0.5, 0.5; 1 to < 2 years, 0.6, 0.6; 2 to < 6 years, 0.8,
0.8; 6 to < 10 years, 1, 1; 10 to < 13 years, 1.2, 1.2; 13 to < 16 years, 1.5, 1.4;
>/= 16 years, 1.7, 1.4.

10. Enrollment inclusion criteria: Adequate liver function, defined as: total bilirubin
liver function due to primary disease).

11. Enrollment inclusion criteria: Evidence of adequate bone marrow function (defined by
ANC >/= 750 and Platelets >/=50,000), unless patient has documented tumor metastasis
to the bone marrow or other condition that results in cytopenia without abnormal
marrow function.

12. Enrollment inclusion criteria: Pulmonary symptoms controlled by medication and pulse
oximetry >/= 92% on room air.

13. Enrollment inclusion criteria: Sexually active males and females of childbearing
potential must agree to use a form of contraception considered effective and medically
acceptable by the Investigator. (Non-childbearing potential defined as pre-menarche,
greater than one year post-menopausal or surgically sterilized).

14. Enrollment inclusion criteria: Confirmation that a cord blood donor which is matched
with the recipient at a 4, 5, or 6/6 HLA class I (serological) and HLA class II
(molecular) antigens.

15. Enrollment inclusion criteria: Signed Informed Consent and if applicable pediatric
assent.

Exclusion Criteria:

1. Screening exclusion criteria: Primary tumors of the central nervous system.

2. Screening exclusion criteria: Chronic corticosteroid dependence that is unable to be
weaned to discontinue.

3. Screening exclusion criteria: Determined by study doctor that patient is unlikely to
meet inclusion criteria after screening.

4. Enrollment exclusion criteria: Uncontrolled arrhythmias or uncontrolled symptoms of
cardiac disease noted by screening history and physical. Patients with known cardiac
dysfunction should have an EF > 40% documented by ECHO.

5. Enrollment exclusion criteria: Patients where the burden of pulmonary metastasis,
location, or bulkiness of disease may cause high morbidity if localized swelling such
as causing uncontrolled symptoms, oxygen dependence, or location near a major bronchi
as determined by investigator.

6. Enrollment exclusion criteria: Pregnant females.

7. Any uncontrolled systemic infection