Adoptive Transfer of Tumor Infiltrating Lymphocytes for Biliary Tract Cancers

Inclusion Criteria:

• Measurable locally advanced, recurrent, or metastatic biliary tract carcinoma (including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, orampullary carcinoma).

• Patients with locally advanced disease should be unresectable by conventionalsurgical approaches.

• Patients with distant metastatic spread must be refractory to approved standardsystemic therapies (such as gemcitabine, cisplatin, or equivalents) if they areeligible to receive these treatments.

• Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest andPreparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-ClinicalStudies) and have available TIL cultures for therapy.

• Patients with 3 or fewer brain metastases that are less than 1 cm in diameter andasymptomatic are eligible. Lesions that have been treated with stereotacticradiosurgery must be clinically stable for 1 month after treatment for the patientto be eligible. Patients with surgically resected brain metastases are eligible.

• Greater than or equal to 18 years of age and less than or equal to age 75

• Able to understand and sign the Informed Consent Document

• Clinical performance status of ECOG 0 or 1

• Life expectancy of greater than three months

• Patients of both genders who are of child-bearing potential must be willing topractice birth control from the time of enrollment on this study and for up to fourmonths after receiving the treatment.

• Serology:

• Seronegative for HIV antibody. (The experimental treatment being evaluated inthis protocol depends on an intact immune system. Patients who are HIVseropositive can have decreased immune-competence and thus be less responsiveto the experimental treatment and more susceptible to its toxicities.)

• Seronegative for hepatitis B antigen, and seronegative for hepatitis Cantibody. If hepatitis C antibody test is positive, then patient must be testedfor the presence of antigen by RT-PCR and be HCV RNA negative.

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

• Hematology

• Absolute neutrophil count greater than 1000/mm3 without the support offilgrastim

• WBC ≥ 3000/mm3

• Platelet count ≥ 100,000/mm3

• Hemoglobin > 8.0 g/dl

• Chemistry

• Serum ALT/AST ≤ to 3.5 times the upper limit of normal

• Serum creatinine ≤ to 1.6 mg/dl

• Total bilirubin ≤ to 2.0 mg/dl, except in patients with Gilbert's Syndrome whomust have a total bilirubin less than 3.0 mg/dl.

• More than four weeks must have elapsed since any prior systemic therapy at the timethe patient receives the preparative regimen, and patients' toxicities must haverecovered to a clinically manageable level (except for toxicities such as alopeciaor vitiligo). (Note: Patients may have undergone minor surgical procedures withinthe past 3 weeks, as long as all toxicities have recovered to grade 1 or less)

Exclusion Criteria:

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

• Any form of primary immunodeficiency (such as Severe Combined ImmunodeficiencyDisease).

• Concurrent opportunistic infections (The experimental treatment being evaluated inthis protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptibleto its toxicities).

• Active systemic infections (e.g.: requiring anti-infective treatment), coagulationdisorders or any other active major medical illnesses.

• History of clinically significant major organ autoimmune disease

• Concurrent systemic steroid therapy.

• History of severe immediate hypersensitivity reaction to any of the agents used inthis study.

• History of active coronary or ischemic symptoms.

• Documented LVEF of less than or equal to 45%; note: testing is required in patientswith:

• Age > 65 years' old

• Clinically significant atrial and or ventricular arrhythmias including but notlimited to: atrial fibrillation, ventricular tachycardia, second or thirddegree heart block or have a history of ischemic heart disease, chest pain.

• Documented FEV1 less than or equal to 60% predicted tested in patients with:

• A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).

• Symptoms of respiratory dysfunction

• Patients who are receiving any other investigational agents.