NY-ESO-1 Specific T Cells After Cyclophosphamide in Treating Patients With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

PRIMARY OBJECTIVES:

I. To confirm the safety and efficacy of cancer-testis antigen (NY-ESO-1) specific T cells
(autologous NY-ESO-1-specific cluster of differentiation [CD]8-positive T lymphocytes) in
patients with advanced synovial sarcoma and myxoid/round cell liposarcoma following
conditioning with high dose cyclophosphamide.

SECONDARY OBJECTIVES:

I. To confirm the persistence of NY-ESO-1 tetramer positive cells in the peripheral blood at
10 weeks after T cell infusion for synovial sarcoma and myxoid/round cell liposarcoma
patients receiving NY-ESO-1 specific T cells following cyclophosphamide conditioning but not
post-infusion interleukin (IL)-2.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) on days -3 and -2 and NY-ESO-1 specific
T cells IV over 60 minutes on day 0. Patients may receive additional infusions at the
discretion of the Principal Investigator (PI).

After completion of study treatment, patients are followed up for up to 12 weeks.

Inclusion Criteria:

INCLUSION CRITERIA FOR SCREENING:

- Medical history including histopathological documentation of sarcoma

- Informed consent and Health Insurance Portability and Accountability Act (HIPAA)
signing

CRITERIA FOR LEUKAPHERESIS:

- NY-ESO-1 expression in tumor by immunohistochemistry (IHC) is not required prior to
screening consent; however, patients must have NY-ESO-1 expression to proceed with
the leukapheresis; additionally patients must also meet the following criteria to
proceed with leukapheresis (any exceptions to this will require prior approval by the
Apheresis director and Principal Investigator):

- Physical exam and Karnofsky performance status

- Laboratory evaluation:

- Complete blood count (CBC), differential and platelet count

- Basic metabolic and hepatic function panels

- Puget Sound Blood Center Recipient Donor Battery Panel

- Pregnancy test for females of child-bearing potential

- Pulse > 45 and < 120

- Weight >= 45 kg

- Temperature =< 38 Celsius (C) (=< 100.4 Fahrenheit [F])

- White blood cell (WBC) >= 2,000

- Hematocrit (HCT) >= 30%

- Platelets >= 75,000

- Research blood including 40 mL of blood in a heparinized tube for peripheral blood
mononuclear cell (PBMC) collection and 10 mL of blood for serum collection (generally
in a red top tube) within 30 days of leukapheresis collection

INCLUSION CRITERIA FOR TREATMENT:

- A diagnosis of synovial sarcoma or myxoid/round cell liposarcoma

- Patients must have "advanced disease"; usually, this will mean metastatic disease;
this may also be multiply recurrent disease or locally advanced disease; locally
advanced disease is defined for this study as disease where a mutilating surgery is
required and the patient is more likely than not to die of their disease despite an
aggressive operation; patients with metastatic disease that has been resected or
radiated are allowed to participate; Response Evaluation Criteria in Solid Tumors
(RECIST) evaluable disease is not necessary for participation

- NY-ESO-1 positive by IHC (for this study, even a small level of positivity is
acceptable); for patients with < 5% NY-ESO-1 by IHC positivity, the level of staining
should be discussed with the patient and they should be informed that this will
likely effect the efficacy of the therapy; this conversation must be documented in
the patient's medical chart

- Human leukocyte antigen (HLA)-A0201 or HLA-A2402

- Zubrod performance status of '0-1'

- All patients must have an electrocardiogram (ECG) within 2 weeks of starting
conditioning

- All patients must have a stress test within 6 months of starting treatment showing no
evidence of cardiac ischemia

- All patients must have an echo or multi gated acquisition scan (MUGA) scan showing
ejection fraction (EF) > 50% and normal troponin and creatine kinase (CK) myoglobin
binding (MB) (echo may be done at the time of stress test as a stress echo); within 6
months of starting treatment; however if the patient has received cardiotoxic
chemotherapy such as Adriamycin, they must have had an echo or MUGA scan since
completing this treatment

- If there is a patient with an NY-ESO-1 expressing soft tissue sarcoma who would be
otherwise eligible for the trial, which is either not synovial sarcoma (SS) or
myxoid/round cell liposarcoma (MRCL) or there is controversy about the diagnosis,
eligibility will be decided by the PI

- Patients must have NY-ESO-1 specific cells already produced or in production; these
cells may be either in the process of their final expansion (for fresh infusion) or
expanded and frozen at the time of enrollment

Exclusion Criteria:

- Patients for whom we are unable to generate NY-ESO-1 specific cells

- Pregnant women, nursing women, and men and women of reproductive ability who are
unwilling to use effective contraception or abstinence; women of childbearing
potential must have a negative pregnancy test within two weeks prior to study entry

- Serum creatinine > 1.6 mg/dL or glomerular filtration rate < 50

- Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3 x upper limit of
normal

- Bilirubin > 1.6 mg/dL

- Prothrombin time > 1.5 x control

- Active symptomatic congestive heart failure

- Clinically significant hypotension (systolic blood pressure [SBP] < 80 mm HG or
symptomatic)

- Newly diagnosed cardiac arrhythmia; patients with an arrhythmia that has been stable
for at least 6 months will be allowed to participate

- Known untreated central nervous system (CNS) metastasis; patients with CNS metastasis
will be allowed on study once treated

- Patients with active systemic infections requiring antibiotics or chronic
maintenance/suppressive therapy; once the infection in question has resolved and
patient is off antimicrobial treatment, patients may participate

- Systemic anticancer treatments (including chemotherapy and biologics) less than 3
weeks prior to T cell therapy; locally directed therapy (e.g. radiation) 2 weeks
prior to cell infusion

- Known clinically significant autoimmune disorders requiring systemic
immunosuppression for control

- Patients who are known to be human immunodeficiency virus (HIV) positive are not
eligible for this study

- Current treatment with steroids

- Known infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); (if a
patient was not tested at the time of their leukapheresis, they must be tested prior
to receiving T cell infusion; if testing was done for leukapheresis, this is adequate
and does not need to be repeated)

- Patients with a known history of proven myocarditis, pericarditis, and/ or
endocarditis