Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI...

This is an interventional treatment trial for Metastatic Melanoma focused on measuring Young TIL, Metastatic Melanoma, Immunotherapy, Adoptive Cell Therapy, Skin Cancer Read More

• INCLUSION CRITERIA:

  1. Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation. The lesion must be of at least 1cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization less than or equal to 7 days).
  2. Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
  3. Greater than or equal to 18 years of age and less than or equal to 66 years of age.
  4. Willing to practice birth control during treatment and for four months after receiving all protocol related therapy.
  5. Life expectancy of greater than three months
  6. Willing to sign a durable power of attorney.
  7. Able to understand and sign the Informed Consent Document
  8. Clinical performance status of ECOG 0 or 1.
  9. Hematology:
• Absolute neutrophil count greater than 1000/mm(3)
• Hemoglobin greater than 8.0 g/dl

• Platelet count greater than 100,000/mm(3)

  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 be less responsive to the experimental treatment and more susceptible to its toxicities.)

• Seronegative for hepatitis B antigen, or hepatitis C antibody or antigen.

  k. Chemistry:

• Serum ALT/AST less than three times the upper limit of normal.
• Calculated creatinine clearance (eGFR) > 50 ml/min.
• 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 3 mg/dl.

l. More than four weeks must have elapsed since any prior systemic therapy at the time of randomization, and patients toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients must have stable or progressing disease after prior treatment.

Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the inclusion criteria.

m. Six weeks must have elapsed since any prior anti-CTLA4 antibody therapy to allow antibody levels to decline.

Note: Patients who have previously received ipilimumab or tremelimumab, anti- PD1 or anti-PD-L1 antibodies, and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

1. Prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen.
2. Women of child-bearing potential who are pregnant or breastfeeding because 10 of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
3. Systemic steroid therapy requirement.
4. 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.
5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
6. 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. History of coronary revascularization or ischemic symptoms.
9. Any patient known to have an LVEF less than or equal to 45%.
10. In patients > 60 years old, documented LVEF of less than or equal to 45%.

11. 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
12. Prior radiation therapy that, in the judgment of the radiation oncologist, precludes the administration of total body irradiation.