CD30 CAR T Cells, Relapsed CD30 Expressing Lymphoma (RELY-30)

To prepare the CD30.CAR T cells, research staff will take some blood from the subject. This
would be drawn as two separate blood collections.

Alternatively, if the subject's blood counts are low, staff may collect the cells needed to
prepare T cells by a pheresis procedure. This procedure will involve placing a needle in both
arms, collecting the cells over 3 to 6 hours during which the subject will be required to lie
relatively still.

After the T cells have been collected, some of them will be activated stimulating them with
antibodies and will then be infected with a retroviral vector (a special virus that can
carries a new gene into cells) containing a new gene called anti-CD30 that will make an
antibody to lymphoma cells. The trained cells are called CD30.CAR T cells. Then, the cells
will be tested to make sure that they kill lymphoma cells that express the CD30 antigen and
not normal cells.

The cells generated will be frozen and stored to give back to the subject.

This is a dose escalation study. This means that at the beginning, patients will be started
on the lowest doses (1 of 3 different levels) of CD30.CAR T Cells. Once that dose schedule
proves safe, the next group of patients will be started at a higher dose. This process will
continue until all 3 dose levels are studied. If the side effects are too severe, the dose
will be lowered or the T cell infusions will be stopped. The risks of harm and discomfort
from the study treatment may bear some relationship to the dose level. The potential for
direct benefit, if any, may also vary with the dose level.

Subjects will be given one injection of CD30.CAR T cells. The injection will be on Day 0. The
subject may be given a dose of Benadryl and Tylenol before the injection of T cells to
minimize any possible allergic reaction. The injection will take 1-10 minutes. The subject
will be monitored in the clinic after each injection for up to 3 hours.

At the discretion of the study doctor, if the subject has stable disease (the lymphoma did
not grow) or there is a reduction in the size of the lymphoma on imaging studies at week 8
after the T-cell infusion or on subsequent evaluations, then the subject can receive up to
six additional doses of the T cells at 8 to 12 weeks intervals. After each T cell injection,
the subject will be monitored as described above.

If the subject is not post autologous transplant they will receive treatment with
cyclophosphamide and fludarabine (chemotherapy drugs) before the CD30.CAR T cells. These
drugs will decrease the numbers of the patient's T cells before the CD30.CAR T cells are
infused. Although the investigators do not expect any effect on the tumor with the dose that
the patient will receive, these drugs are part of many regimens that are used to treat
lymphoma or leukemia.

To learn more about the way the CD30.CAR T cells are working and how long they last in the
body, extra blood will be drawn. On the day that the subject receives the cells, blood will
be taken before the cells are given and several hours afterwards. Other blood will be drawn
at 1 week, 2 weeks, 3 weeks (optional), 4 weeks, 6 weeks and 8 weeks, every 3 months for 1
year, every 6 months for 4 years, then yearly for a total of 15 years.

PROCUREMENT Inclusion Criteria:

1. Diagnosis of relapsed/refractory HL or NHL.

2. CD30 positive tumor as assayed in a CLIA certified pathology laboratory (result can be
pending at this time)

3. Hgb ≥ 7.0 (may be a transfused value)

4. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.

5. Karnofsky or Lansky score of > 60%

TREATMENT Inclusion Criteria:

1. Diagnosis of relapsed/refractory HL or NHL.

2. CD30-positive tumor as assayed in a CLIA certified pathology laboratory.

3. Age 16 to 75 for the first three patients on a dose level; thereafter, if no DLT,
patients aged 12 to 75 can be treated on that dose level.

4. Bilirubin 1.5 times or less than the upper limit of normal.

5. AST 3 times or less than the upper limit of normal.

6. Estimated GFR > 70 mL/min.

7. Pulse oximetry of > 90% on room air

8. EKG shows no significant arrhythmias

9. Karnofsky or Lansky score of > 60%.

10. Available autologous T cells with greater than or equal to 15% expression of CD30CAR
determined by flow-cytometry.

11. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.

12. Adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50% of
expected corrected for hemoglobin.

13. Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after the study is concluded. The
male partner should use a condom.

14. Informed consent explained to, understood by and signed by patient or guardian.

PROCUREMENT Exclusion Criteria:

1. Active infection with HIV or HTLV (can be pending at this time).

2. Active bacterial, fungal or viral infection.

TREATMENT Exclusion Criteria:

1. Currently receiving any investigational agents or received any tumor vaccines within
the previous six weeks.

2. Received anti-CD30 antibody-based therapy within the previous 4 weeks.

3. Subjects with rapidly progressive disease, defined as kinetic failure to previous
chemotherapy.

4. Bulky disease (defined as a 10 cm mass or mediastinal disease with a transverse
diameter exceeding 33% of the transthoracic diameter).

5. History of hypersensitivity reactions to murine protein-containing products.

6. Pregnant or lactating.

7. Tumor in a location where enlargement could cause airway obstruction.

8. Current use of systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of
prednisone or higher.

9. Active hemorrhagic cystitis.

10. Active bacterial, viral or fungal infection.

11. Symptomatic cardiac disease (NYHA Class III or IV disease).