Anti-ESO (Cancer/Test Antigen) mTCR-transduced Autologous Peripheral Blood Lymphocytes and Combination Chemotherapy in Treating Patients With Metastatic Cancer That Expresses NY-ESO-1

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the administration of anti-ESO (cancer/test
antigen) mTCR (T cell receptor)-engineered peripheral blood lymphocytes (anti-thyroglobulin
mTCR-transduced autologous peripheral blood lymphocytes) plus high-dose aldesleukin following
a nonmyeloablative lymphoid depleting preparative regimen in human leukocyte antigen (HLA)-A2
positive patients with metastatic cancer expressing the ESO antigen.

SECONDARY OBJECTIVES:

I. Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.

II. Determine the objective response rate by Response Evaluation Criteria in Solid Tumors
(RECIST) criteria.

OUTLINE:

Patients receive standard cyclophosphamide intravenously (IV) over 1 hour on days -7 to -6
and fludarabine phosphate via intravenous piggy back (IVPB) over 30 minutes on days -5 to -1
followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood
lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately
every 8 hours on days 0-4. Patients also receive filgrastim subcutaneously (SC) on days 1-4.

After completion of study treatment, patients are followed up at 6 weeks, annually for 5
years, and then periodically for 10 years thereafter.

Inclusion Criteria:

- Measurable metastatic cancer that expresses NY ESO-1 as assessed by one of the
following methods: reverse transcriptase-polymerase chain reaction (RT-PCR) on tumor
tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with
ESO

- Confirmation of diagnosis of metastatic cancer by the Laboratory of Pathology at the
Montefiore Medical Center

- Patients must have previously received systemic standard care (or effective salvage
chemotherapy regimens) for metastatic disease, if known to be effective for that
disease, and have been either non-responders (progressive disease) or have recurred

- 3 or fewer brain metastases; Note: if lesions are symptomatic or greater than or equal
to 1 cm each, these lesions must have been treated and stable for 3 months for the
patient to be eligible

- More than four weeks must have elapsed since any prior systemic therapy at the time
the patient receives the preparative regimen, and patients' toxicities must have
recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo);
Note: patients may have undergone minor surgical procedures within the past 3 weeks,
as long as all toxicities have recovered to grade 1 or less or as specified in the
eligibility criteria

- Eight weeks must have elapsed from the time of any antibody therapy that could affect
an anti-cancer immune response, including anti-cytotoxic T-lymphocyte-associated
protein 4 (CTLA 4) therapy, at the time the patient receives the preparative regimen
to allow antibody levels to decline; Note: patients who have previously received
ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal
colonoscopy with normal colonic biopsies

- Willing to sign a durable power of attorney

- Able to understand and sign the informed consent document

- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1

- Life expectancy of greater than three months

- Patients must be HLA-A*0201 positive

- Patients of both genders must be willing to practice birth control from the time of
enrollment on this study and for up to four months after cells are no longer detected
in the blood

- Serology:

- Seronegative for human immunodeficiency virus (HIV) antibody; (the experimental
treatment being evaluated in this protocol depends on an intact immune system;
patients who are HIV seropositive can have decreased immune-competence and thus
be less responsive to the experimental treatment and more susceptible to its
toxicities)

- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody;
if hepatitis C antibody test is positive, then patient must be tested for the
presence of antigen by RT-PCR and be hepatitis C virus (HCV) ribonucleic acid
(RNA) negative

- Women of child-bearing potential must have a negative pregnancy test because of the
potentially dangerous effects of the treatment on the fetus

- Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim

- White blood cell (WBC) >= 3000/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin > 8.0 g/dl

- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< to 2.5 times
the upper limit of normal

- Serum creatinine =< to 1.6 mg/dl

- Total bilirubin =< to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must
have a total bilirubin less than 3.0 mg/dl

Exclusion Criteria:

- Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the treatment on the fetus or infant

- Any form of primary immunodeficiency (such as severe combined immunodeficiency
disease)

- Active systemic infections, coagulation disorders or other major medical illnesses of
the cardiovascular, respiratory or immune system, myocardial infarction, cardiac
arrhythmias, obstructive or restrictive pulmonary disease

- Concurrent opportunistic infections (the experimental treatment being evaluated in
this protocol depends on an intact immune system; patients who have decreased immune
competence may be less responsive to the experimental treatment and more susceptible
to its toxicities)

- Concurrent systemic steroid therapy

- History of severe immediate hypersensitivity reaction to any of the agents used in
this study

- History of coronary revascularization or ischemic symptoms

- History of or active central nervous system (CNS) or peripheral nerve stimulation
(PNS) involvement

- Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%;
testing is required in patients with:

- Clinically significant atrial and/or ventricular arrhythmias including but not
limited to: atrial fibrillation, ventricular tachycardia, second or third degree
heart block

- Age >= 60 years old

- Pulmonary function testing in patients with:

- A prolonged history of cigarette smoking (20 pk/yr of smoking within the past two
years)

- Symptoms of respiratory dysfunction