Phase 1/2 Study of Metastatic Renal Cancer Using T-Cells Transduced With a T-Cell Receptor Which Recognizes TRAIL Bound to the DR4 Receptor

• INCLUSION CRITERIA:

  1. Measurable metastatic clear cell renal cancer. Histologic diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
  2. Patients must have previously received at least one systemic standard care regimens and have progressed or be found to be intolerant of standard therapies.
  3. Greater than or equal to 18 years of age.
  4. Willing to sign a durable power of attorney
  5. Able to understand and sign the Informed Consent Document
  6. Clinical performance status of ECOG 0 or 1.
  7. Life expectancy of greater than three months.
  8. Patients of both genders must be willing to practice birth control during and for four months after receiving the preparative regimen.

  9. Serology:

     1. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immunecompetence, and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
     2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
     3. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

  10. Hematology:

      1. Absolute neutrophil count greater than or equal to 1000/mm3 without the support of filgrastim.
      2. WBC greater than or equal to 3000/mm3.
      3. Platelet count greater than or equal to 100,000/mm3.
      4. Hemoglobin greater than or equal to 8.0 g/dl.

  11. Chemistry:

      1. Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
      2. Serum creatinine less than or equal to 1.6 mg/dl.
      3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  12. 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 alopecia or skin rash, which must have recovered to a grade 2 or less).
  13. Patients who have previously received anti-CTLA4 antibody must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
2. 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.
3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
4. 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.)
5. Concurrent systemic steroid therapy
6. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
7. History of coronary revascularization or ischemic symptoms

8. Documented LVEF less than or equal to 45%. LVEF will be evaluated in patients with:

   1. History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
   2. Age greater than or equal to 60 years old

9. Documented FEV1 less than or equal to 60% predicted. Screening pulmonary function testing will be done in patients with:

   1. A prolonged history of cigarette smoking (20 pk/year of smoking, who have not quit within the past 2 years).
   2. Symptoms of respiratory dysfunction
10. Patients who have a history of more than two CNS metastases.
11. Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or shows significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.