Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian

INCLUSION CRITERIA

1. Able to understand and sign the Informed Consent Form.
2. Pathology confirmed epithelial Ovarian/Fallopian Tube/Primary Peritoneal carcinomatosis.
3. For ovarian/peritoneal carcinoma: Platinum- resistant or platinum refractory disease (platinum-resistant disease is defined as disease-progression within 6 months of completion of prior platinum containing regimen, whereas platinum refractory disease is defined as disease progression while on platinum containing regimen or within 3 months from first line, adjuvant chemotherapy).
4. Received and exhausted standard of care therapies for recurrent ovarian cancer and further chemotherapy lines have no proven added value. (For platinum resistant disease, received no more than 3 prior chemotherapy lines, whereas for platinum refractory disease received no more than 2 previous chemotherapy lines).
5. Patients must have at least one lesion that is resectable for TIL generation.
6. Have measurable disease per RECIST 1.1.
7. Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 6 weeks.
8. Greater than or equal to 18 years of age.
9. For Patients with child bearing potential, willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
10. Life expectancy of greater than three months
11. Performance status of ECOG 0 or 1

12. Adequate organ function defined by lab test results:

    Hematology:

    Absolute neutrophil count greater than 1000/mm3 without support of filgrastim Normal WBC greater than 3000/mm3. Hemoglobin greater than 9.0 g/dL Platelet count greater than 100,000/mm3

    Serology:

    Seronegative for HIV antibody. Seronegative for Hepatitis B or Hepatitis C (patients who recovered from previous infection and have no detected HBSAg or HCV RNA are allowed).

    Chemistry:

    Serum ALT/AST less than three times the upper limit of normal (ULN). Serum creatinine less than or equal to 1.6 mg/dL Total bilirubin no more than 1.5 times the ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dL.

13. Negative pregnancy test in women of child bearing potential.
14. 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 toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.

Note: As described in the Study Population section in the synopsis, before entering the trial, the medical team will present other available experimental therapies to the patient for her consideration.

SUBJECT EXCLUSION CRITERIA

1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant. (Note: Pregnancies occurring in patients with Ovarian cancer are very rare, but possible. For this reason, ELIM has decided to retain the sections dealing with possible cases of pregnancy during the study.)
2. Systemic steroid therapy required (patients who require replacement therapy for adrenal insufficiency may be enrolled if steroid treatment dose do not exceed 10 mg of prednisone or equivalent).
3. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
5. 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.)
6. History of severe immediate hypersensitivity reaction to any of the agents used in this study , including history of an anaphylactic reaction to penicillin or gentamicin
7. History of coronary revascularization or ischemic heart disease.
8. Any patient known to have an LVEF less than or equal to 50 percent.
9. Documented LVEF of less than or equal to 50 percent tested in patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
10. Documented FEV1 and DLCO (relative to predicted) less than or equal to 60 percent.