Study of Adoptive Immunotherapy Using Autologous CD8+ NY-ESO-1-Specific T Cells and the NY-ESO-1 Immunostimulatory Agents LV305 or CMB305 For Patients With Sarcoma

Leukapheresis (Apheresis):

If you are found to be eligible to take part in this study, some of your blood cells will be
collected by leukapheresis. For this procedure, you will need to stay seated in a chair and
keep both arms still for up to 4 hours. During this process, your blood will flow into the
machine and then directly back into your bloodstream through the second line. Blood will be
drawn from 1 arm through a catheter (needle and tube) connected to the leukapheresis machine.
Inside the machine, the white blood cells will be separated from the rest of the blood cells
and collected in a sterile bag. Then, the rest of the blood cells will be returned through a
catheter to your other arm. A blood thinner called citrate will be added to the blood as it
enters the machine in order to lower the risk of your blood clotting in the machine.

If you cannot tolerate the leukapheresis procedure, this blood may be drawn by vein (like a
regular blood draw).

Researchers may also used white blood cells previously collected from you when and if you
consented to take part in protocol PA14-0138.

The blood will be sent to the laboratory where the T cells will be grown. It will take about
6-8 weeks for your T cells to grow in the laboratory.

It is possible that you will need to have a central venous catheter (CVC) placed for this
procedure. A CVC is a sterile flexible tube that will be placed into a large vein while you
are under local anesthesia. Your doctor will explain this procedure to you in more detail,
and you will be required to sign a separate consent form.

It is possible that your T cells may not grow and then cannot be infused back into you. If
this happens with your cells, the study doctor will talk to you about options available to
you. One option may be that you will have another leukapheresis procedure done and another
attempt is made to make the changed T cells.

Study Groups:

You will be assigned to a study group (also called a Cohort) depending on when you enroll in
this study:

- If you are in Cohort 0, you will receive modified T cells.

- If you are in Cohort 1, you will receive modified T cells and LV305.

- If you are in Cohort 2, you will receive modified T cells, LV305, and G305.

Study Drug and T cell Administration:

You will have 1 infusion of chemotherapy (cyclophosphamide) before you receive your changed T
cells. The chemotherapy will help your body get ready to receive your changed T cells.

Negative days are the days before you receive the T cells and positive days are the days
after you receive the T cells. Day 0 is the day you receive the T cells.

On Day -2:

- You will receive cyclophosphamide by vein over about 30-60 minutes.

- If you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a
pregnancy test.

On Day 0, you will receive the modified T cells by vein over about 60 minutes. You will be
admitted to the hospital for the infusion, and your study doctor will tell you for how many
days you will remain in the hospital after you receive the changed T cells. You will be
watched closely for 24 hours after your T cell infusion to check for any reactions.

Starting within 6 hours after the modified T cell infusion and then 2 times each day after
that for 14 days, you will receive aldesleukin as an injection into your skin around your
abdomen. You will be taught how to give yourself these injections.

If you are in Cohort 1, you will receive injections of LV305 on Days 1, 22, 43, and 64.

If you are in Cohort 2, you will receive injections of LV305 on Days 1, 14, 43, and 70. You
will also receive injections of G305 on Days 29, 57, 85. During the first year of follow-up,
you will continue receiving "boost" injections of G305 at each scanned visit to help your
immune system.

You will also be given standard drugs 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 T cells 1 time. If you are in Cohort 1 or 2, you may receive injections
of study drug for up to 85 days after the T cell infusion. You will have study visits for up
to 168 days after the T cell infusion.

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 2 weeks before you receive the T cells:

- You will have a physical exam.

- Blood (about 5 1/2 tablespoons) will be drawn for will be drawn for routine tests,
immune system tests, and tests on how long the T-cells survive in your body.

- You will have a CT scan to check the status of the disease.

On Day 0:

- You will have an EKG before the infusion.

- You will have a physical exam before the infusion.

- Blood (about 5 1/2 tablespoons) will be drawn for will be drawn for routine tests,
immune system tests, and tests on how long the T-cells survive in your body.

On Days 1 and 3, blood (about 5 1/2 tablespoons) will be drawn for will be drawn for routine
tests, immune system tests, and tests on how long the T-cells survive in your body.

Beginning with Day 7, you will have study visits every week for the first 12 weeks (until Day
85), then every 4 weeks for the next 12 weeks (until Day 168). At these visits:

- You will have a physical exam.

- Blood (about 5½ tablespoons) will be drawn for routine tests, immune system tests, and
tests on how long the T-cells survive in your body.

- Between Day 35 and 42 and again between Day 77 and 84, you will have a CT scan to check
the status of the disease.

If you are in Cohort 1 or 2 and you can become pregnant, you will have a pregnancy test
before you receive LV305 each time.

After 6 months, blood (about 5 1/2 tablespoons) will be drawn approximately every 3 months
for routine tests, immune system tests, and tests on how long the T-cells survive in your
body and a CT scan will be done to check the status of the disease, for up to 24 months after
the end of treatment, unless the disease gets worse or you begin a new treatment.

At 1 and 2 years after the first injection of LV305, blood (about 1 teaspoon) will be drawn
to learn how much LV305 is in your blood. If you still have LV305 in your blood at 2 years,
this test will be repeated 1 time a year until you no longer have LV305 in you blood.

Long term follow up:

You will be called every 3 months after any time that the disease gets worse until 2 years
after the first study injection. You will be asked about how you are doing and any other
treatments you may have received. The calls should take about 5-10 mins.

Inclusion Criteria:

1. Histopathologic documentation of synovial sarcoma or myxoid liposarcoma with the
diagnosis of advanced or recurrent disease who have received prior standard
chemotherapy

2. Tumor expression of NY-ESO-1 (2+ staining or > 25%) by IHC. If no archival tissue is
available patient will have to undergo a biopsy for NY-ESO-1 testing.

3. Male or female subjects >/= 18 years of age.

4. Expression of HLA-A*0201

5. ECOG/ Zubrod performance status of '0-1'

6. Life expectancy > 6 months

7. ECG without evidence of clinically significant arrhythmia or ischemia

8. Women of childbearing potential (WOCBP) must be using at least one highly effective or
two effective accepted methods of contraception to avoid conception throughout the
study in such a manner that the risk of pregnancy is minimized. Suggested precautions
should be used to minimize the risk or pregnancy for at least 1 month before start of
therapy, and while women are on study for up to 3 months after T cell infusion and/or
at least 3 months after the study agents LV305 or CMB305 are stopped. WOCBP include
any female who has experienced menarche and who has not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is
not postmenopausal

9. Men must be willing and able to use an acceptable method of birth control such as
latex condom during the dosing period and for at least 3 months after completion of
the study agent administration (T cell infusion and/or LV305 or CMB305) if their
sexual partners are WOCBP.

10. Willing and able to give informed consent.

11. (Prior to treatment) Note: evaluate at least 1 week before T cell infusion. a.
Adequate venous access - consider PICC or central line. b. ECOG/Zubrod performance
status of '0-1. c. Bi-dimensionally measurable disease by palpation on clinical exam,
or radiographic imaging (CT scan). d. At least 4 Weeks must have elapsed since the
last chemotherapy, immunotherapy, radiotherapy or major surgery. At least 6 Weeks for
nitrosoureas, mitomycin C and liposomal doxorubicin. e. Toxicity related to prior
therapy must either have returned to irreversible. f. Persons of reproductive potential must agree to use and utilize an
adequate method of contraception throughout treatment and for at least 3 months after
study drug is stopped. g. Willing and able to give informed consent.

Exclusion Criteria:

1. Patients with active infections or oral temperature > 38.2 C within 72 hours of
Leukapheresis. The procedure may be deferred.

2. Investigational therapy within 3 weeks

3. Prior administration of other NY-ESO-1 targeting immunotherapeutics

4. Significant immunosuppression from concurrent, recent ( treatment with systemic corticosteroids at any dose, or other immunosuppressive
medications such as methotrexate, cyclosporine, azathioprine (antihistamines,
non-steroidal anti-inflammatory drugs and aspirin permitted) or conditions such as
common variable hypogammaglobulinemia or exposures such as large field radiotherapy

5. Cancer therapies, including chemotherapy, radiation, biologic, or kinase inhibitors,
G-CSF, GM-CSF within 4 weeks prior

6. Psychiatric, other medical illness or other condition that in the opinion of the PI
prevents compliance with study procedures or ability to provide valid informed consent

7. Significant autoimmune disease with the exception of alopecia, vitiligo,
hypothyroidism or other conditions that have never been clinically active or were
transient and have completely resolved and require no ongoing therapy

8. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or
NYHA Grade III or IV heart failure

9. Inadequate organ function including: a. Marrow: Peripheral blood leukocyte count (WBC)
< 3000/mm^3, absolute neutrophil count hemoglobin < 10 gm/dL b. Hepatic: Alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) > 2.5 x ULN, total serum bilirubin > 1.5 x ULN (Patients with
Gilbert's Disease may be included if their total bilirubin is Creatinine > 1.5 x ULN d. Other: INR (prothrombin time ratio) or partial
thromboplastin time (PTT) > 1.5 x ULN (Please Note: Patients with Hct < 30%, WBC
<2500/mm/^3and platelets <50,000/mm^3 immediately prior to Leukapheresis. The
procedure may be deferred.)

10. History of other cancer within 3 years (except non-melanoma cutaneous malignancies and
cervical carcinoma in situ)

11. Positive screening tests for HIV, Hep B, Hep C, active tuberculosis or recent (< 2
week ago) clinically significant infection or evidence of active HIV, Hep B, or Hep C.
(Note: If positive results are not indicative of true active or chronic infection, the
patient can be treated.)

12. Brain metastases considered unstable as: a. Without confirmed stability over 60 days
in patients previously treated with prior surgery or radiation; OR b. Associated with
symptoms and/or findings; OR c. Requiring corticosteroids or anticonvulsants in the
prior 60 days

13. Pregnant, planning to become pregnant, or breast feeding

14. Known allergy(ies) to any component of CMB305 or LV305

15. Men or women of reproductive ability who are unwilling to use effective contraception
and women of childbearing potential who are unwilling to undergo pregnancy testing
before and during the study.

16. Clinically significant pulmonary dysfunction, as determined by medical history and
physical exam. Patients so identified will undergo pulmonary functions testing and
those with FEV1 < 2.0 L or DLco (corr for Hgb) < 75% will be excluded.

17. Significant cardiovascular abnormalities as defined by any one of the following: a.
Congestive heart failure, b. Clinically significant hypotension, c. Symptoms of
coronary artery disease, d. Presence of cardiac arrhythmias on EKG requiring drug
therapy, e. Ejection fraction < 50 % (dobutamine stress echo).

18. Active and untreated central nervous system (CNS) metastasis

19. Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded
from this study, as are patients with a history of autoimmune disease (e.g. Systemic
Lupus Erythematosus, vasculitis, infiltrating lung disease) whose possible progression
during treatment would be considered by the Investigator to be unacceptable.

20. Positive screening tests for HIV, Hep B, and Hep C. If positive results are not
indicative of true active or chronic infection, the patient can be treated.

21. Steroids are not permitted 3 days prior to T cell infusion and concurrently during
therapy.

22. No prisoners or children will be enrolled on this study.