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Investigator(s):
Steven A. Rosenberg, M.D., Ph.D. Principal Investigator Phone: 1-866-820-4505 (Toll Free) ncisbirc@mail.nih.gov
Referral Contact(s):
Linda Williams, R.N. Research Nurse Phone: 1-866-820-4505 (Toll Free) Fax: 301-451-1927 ncisbirc@mail.nih.gov	June A. Kryk, R.N. Research Nurse Phone: 1-866-820-4505 (Toll Free) Fax: 301-451-1927 ncisbirc@mail.nih.gov

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Primary Eligibility:

• Pathologically confirmed metastatic cancer that expresses NY-ESO-1 as assessed by one of the following methods:
  • RT-PCR on tumor tissue
  • Immunohistochemistry of resected tissue
  • Serum antibody reactive with ESO
• Patients with melanoma or renal cell cancer must have previously received high-dose aldesleukin AND have either progressive or recurrent disease
• Patients with any other histologies 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 either progressive or recurrent disease
• HLA-A*0201 positive
• Recovered from all prior therapy
• No concurrent systemic steroid therapy
• ECOG performance status 0–1
• Absolute neutrophil count > 1,000/mm³ (without filgrastim [G-CSF] support)
• WBC > 3,000/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 8 g/dL
• Serum ALT/AST ≤ 2.5 x upper limit of normal
• Total bilirubin ≤ 1.5 mg/dL (< 3 mg/dL in patients with Gilbert’s syndrome)
• Serum creatinine ≤ 1.6 mg/dL
• Not pregnant or nursing; fertile patients must use effective contraception during and for 4 months after completion of study treatment
• Normal colonoscopy with normal colonic biopsies required in patients who received prior MDX-010 or ticilimumab
• HIV antibody negative
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative, unless antigen negative
• No coagulation disorders
• No medical condition that would preclude study participation
• No history of severe immediate hypersensitivity reaction to any of the agents used in this study
• LVEF > 45% in patients meeting any of the following criteria:
  • History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias
  • Aged ≥ 60 years
• FEV₁ > 60% predicted in patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction

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Treatment Plan:

Patients are stratified according to histology (melanoma or renal cell cancer vs other).

Leukapheresis and cell preparation:
• Patients undergo leukapheresis to obtain peripheral blood mononuclear cells which are subsequently cultured in the presence of anti-CD3 (OKT3) and aldesleukin and transduced by exposure to anti-NY-ESO-1 TCR retroviral vector

Lymphodepleting preparative regimen:
• Patients receive cyclophosphamide IV over 1 hour on Days -7 and -6 and fludarabine phosphate IV over 30 minutes on Days -5 to -1

Cell infusion:
• Patients receive anti-NY-ESO-1 TCR gene-engineered peripheral blood lymphocytes IV over 20–30 minutes on Day 0 and filgrastim (G-CSF) subcutaneously daily beginning on Day 1 and continuing until blood counts recover

High-dose aldesleukin:
• Patients receive high-dose aldesleukin IV over 15 minutes 3 x daily on Days 0–4 (maximum of 15 doses)


• Patients may receive 1 retreatment course beginning 6–8 weeks after the last dose of aldesleukin



• Blood is collected periodically for immunological monitoring of cell function by FACS and tetramer analysis immunological assays, and RT-PCR; in vivo survival of TCR gene-engineered peripheral blood lymphocytes is assessed by PCR analysis



• After completion of study therapy, patients are followed periodically for 15 years

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Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 12/5/08
Updated: 11/14/08