Study Comparing TIL to Standard Ipilimumab in Patients With Metastatic Melanoma

In this randomized controlled phase III study the investigators will evaluate whether TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 can result in an improved progression free survival when randomly compared to ipilimumab in 168 stage IV melanoma patients. A health technology assessment (HTA) will be performed to evaluate the impact of the TIL treatment on patients and organizational processes and cost-effectivity.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Histologically confirmed unresectable AJCC stage III or stage IV melanoma
* Patients must have metastatic melanoma with a resectable metastatic lesion(s) of sufficient size (≥ 2-3 cm in total) and must be willing to undergo such a resection for experimental purposes.
* Patients should have received maximum one line of systemic therapy (except for ipilimumab) for unresectable or metastatic melanoma.\[
* Patients must be ≥ 18 years and ≤ 75 years of age and must have measurable disease by CT or MRI per RECIST 1.1 criteria (in addition to the resected lesion).
* Patients must have a clinical performance status of ECOG 0 or 1.
* Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen.
* Patients must be able to understand and sign the Informed Consent document.

Exclusion Criteria:

* Life expectancy of less than three months.
* Patients with metastatic ocular/ mucosal or other non-cutaneous melanoma.
* Adjuvant treatment with ipilimumab within 6 months prior to randomization.
* Requirement for immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to randomization.
* Patients who have a more than two CNS metastases.
* Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or show significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.
* All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less.
* Women who are pregnant or breastfeeding, because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
* Any active systemic infections, coagulation disorders or other active major medical illnesses.
* Any autoimmune disease

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