T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer

This is an interventional treatment trial for Advanced Non-Small Cell Lung Cancer focused on measuring Metastatic, Non-Small Cell Lung Cancer, NSCLC, Lung Cancer Read More

• INCLUSION CRITERIA:

  1. Measurable metastatic (stage IV) or unresectable non-small cell lung cancer (including but not limited to squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinomas) with at least one lesion that is resectable for TIL generation. (Note: neuroendocrine tumors are not eligible.)
  2. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
  3. All patients must have had at least one appropriate first line systemic therapy and progressed.
  4. Clinical performance status of ECOG 0 or 1.
  5. Age Greater than or equal to 18 years of age and less than or equal to 70 years of age.
  6. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.
  7. Willing to sign a durable power of attorney
  8. Able to understand and sign the Informed Consent Document

I. Hematology:

• Absolute neutrophil count greater than 1000/mm3 without support of filgrastim
• Normal WBC (> 2500/mm3).
• Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this cut-off.

• Platelet count greater than 80,000/mm3

  j. Serology:

• 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 immune competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.)

• Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RTPCR and be HCV RNA negative.

  k. Chemistry:

• Serum ALT/AST less than or equal to2.5 times the upper limit of normal.
• Serum creatinine less than or equal to 1.6 mg/dl.

• Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert s Syndrome, who must have a total bilirubin less than or equal to 3 mg/dl.

  l.Women of child-bearing potential must be willing to undergo a pregnancy testprior to the start of treatment because of the

potentially dangerous effects of the treatment on the fetus.

m. Patients must have completed any prior systemic therapy at the time of enrollment.

Note: Patients may have undergone minor surgical procedures or local radiotherapy within the past 4 weeks, as long as related major organ toxicities have recovered to grade 1 or less.

n. More than two weeks must have elapsed since any prior palliation for major bronchial occlusion or bleeding at the time the patient receives the preparative regimen, and patient s toxicities must have recovered to a grade 1 or less.

o. Subjects must be co-enrolled in protocol 03-C-0277

EXCLUSION CRITERIA:

1. Women who are breastfeeding because of the potentially dangerous effects of the treatment on infant.
2. Ongoing need for pharmacological immunosuppression, including steroids
3. Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active or uncompensated major medical illnesses.
4. Major bronchial occlusion or bleeding not amenable to palliation.

5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency

   Disease and AIDS).

6. 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.)
7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
8. For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.
9. For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%

10. Any of the following will exclude patients from the high-dose aldesleukin arm, but may be eligible for the low-dose aldesleukin arm:

    • Greater than 2 invasive thoracic procedures
    • Poor exercise tolerance
    • Greater than 66 years of age
11. Clinically significant patient history which in the judgment of the Principal Investigator would compromise the patient s ability to tolerate high-dose.
12. Patients who are receiving any other investigational agents.