Background:
The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells.
Objective:
The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe.
Eligibility:
\- Adults age 18-72 with NSCLC who have a tumor that can be safely removed.
Design:
* Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. * Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.
Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.
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.)
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.
All patients must have had at least one appropriate first line systemic therapy and progressed.
Clinical performance status of ECOG 0 or 1.
Participants who are nursing because of the potentially dangerous effects of the treatment on the infant.
Ongoing need for pharmacological immunosuppression, including steroids
Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active or uncompensated major medical illnesses
Major bronchial occlusion or bleeding not amenable to palliation.
Parallel
Aldesleukin
DrugAldesleukin 720,000 (Arm 1) or 72,000 (Arm 2) IU/kg IV (based on total body weight) over 15 minutes every 8 hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to a maximum of 9 doses in Arm 1 and 12 doses in Arm 2.
Fludarabine
DrugDays -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide
DrugDays -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with Mesna 15 mg/kg/day X 2 days over 1 hour.
Young TIL
Biological/VaccineDay 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes.
Response rate
Percentage of patients who have a clinical response to treatment (objective tumor regression)
Phenotypic and functional characteristics of TIL
Find in vitro characteristics of the infused cells which correlate with in vivo antitumor activity. Evaluation of the activity, specificity, and telomere length of infused TIL.
Frequency and severity of treatment-related adverse events
Aggregate of all adverse events, as well as their frequency and severity
Feasibility of generating TIL from patients with NSCLC
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