NY-ESO-1-Specific T-cells in Treating Patients With Advanced NY-ESO-1-Expressing Sarcomas Receiving Palliative Radiation Therapy

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity of NY-ESO-1-specific T cells when given following
high-dose, hypo-fractionated palliative radiation to patients with advanced NY-ESO-1
expressing sarcomas.

SECONDARY OBJECTIVES:

I. To look for preliminary evidence of systemic efficacy of NY-ESO-1-specific T-cell therapy
following radiation on non-radiated tumors.

II. To determine whether radiation increases trafficking of adoptively transferred
NY-ESO-1-specific T cells by comparing tumor biopsy specimens from radiated and non-radiated
tumors.

OUTLINE:

Patients undergo palliative radiation therapy at the discretion of the treating radiation
oncologist. Patients then receive NY-ESO-1-specific T cells intravenously (IV) over 60
minutes 2-3 days after completion of radiation therapy.

After completion of study treatment, patients are followed up weekly for 2 weeks, at 4-6, 8,
10, and 12 weeks, and then for up to 6 months.

Inclusion Criteria:

INCLUSION CRITERIA FOR SCREENING:

- Histopathological documentation of sarcoma

- Patients must express NY-ESO-1 in their tumor by immunohistochemistry (IHC) (> 5%)
prior to leukapheresis

- For leukapheresis, patients must meet the following criteria (any exceptions to this
will require prior approval by the apheresis director and principal investigator
[PI]):

- Pulse > 45 or < 120

- Weight >= 45 kg

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

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

- Hematocrit (HCT) >= 30%

- Platelets >= 75,000

INCLUSION CRITERIA FOR TREATMENT:

- A diagnosis of a metastatic or unresectable sarcoma

- Patient must have a biopsy-accessible tumor to be radiated

- Patient must have consulted with a radiation oncologist who is planning radiation;
their radiation oncologist should have documented plans to administer a dose of at
least 30 Gy in 5 or fewer fractions

- Human leukocyte antigen (HLA) type A0201 or A2402

- Zubrod (Eastern Cooperative Oncology Group [ECOG]) performance status of '0-2'

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

- All patients must have an echo or multigated acquisition (MUGA) scan showing ejection
fraction (EF) > 50% and normal troponin and creatine kinase MB (CK MB) performed
within 90 days of starting treatment

Exclusion Criteria:

EXCLUSION CRITERIA FOR SCREENING:

- Patients who do not meet the above inclusion criteria will not receive leukapheresis

EXCLUSION CRITERIA FOR TREATMENT:

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

- Pregnant women, nursing women, 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

- Inadequate renal function as indicated by serum creatinine >= 1.5 times the upper
limit of normal

- Inadequate liver function as indicated by total bilirubin >= 1.5 times the upper
limit of normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >= 2.5 times the
upper limit of normal

- Active symptomatic congestive heart failure

- Clinically significant hypotension

- Newly diagnosed cardiac arrhythmia; patients with an arrhythmia that has been stable
for at least 3 months will be allowed to participate

- Known untreated central nervous system (CNS) metastasis

- Patients with systemic infections requiring antibiotics or chronic
maintenance/suppressive therapy

- Patients receiving systemic anticancer therapy (chemotherapy, "biologics",
immunotherapy) less than 2 weeks prior to starting radiation

- Clinically significant autoimmune disorders requiring on-going systemic
immune-suppression for control

- Patients with acquired immunodeficiency syndrome (AIDS) or who are known to be human
immunodeficiency virus (HIV) positive are not eligible for this study; testing may
have been done up to 3 months prior to treatment

- Current treatment with steroids

- Known infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); testing may
have been done up to 3 months prior to treatment