Background:
* Metastatic ocular melanoma (OM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic OM is classified as an orphan disease and there are currently few clinical trial options for these patients. Thus, novel systemic approaches are desperately needed.
* Administration of autologous tumor infiltrating lymphocytes (TIL) generated from resected metastatic cutaneous melanoma can induce objective long-term tumor responses.
* Minimally invasive, safe, and effective surgical approaches have been developed in the Surgery Branch to procure liver tumor tissue for TIL generation.
Objectives:
* To determine whether autologous Young TIL infused with or without the administration of high-dose aldesleukin may result in clinical tumor regression in patients with metastatic ocular melanoma receiving a non-myeloablative lymphoid depleting preparative regimen.
* To study immunologic correlates associated with Young TIL therapy for ocular melanoma.
* To determine the toxicity of this treatment regimen.
Eligibility:
* Patients with metastatic ocular melanoma who are greater than or equal to 16 years of age, and are physically able to tolerate non-myeloablative chemotherapy. Patients who can tolerate high-dose aldesleukin will receive it following cell infusion; those who cannot tolerate high-dose aldesleukin due to medical comorbidities or refuse high dose aldesleukin will receive cell infusion without aldesleukin.
* There is no requirement for prior systemic therapies, given the lack of known effective systemic treatments for metastatic OM.
Design:
* Patients will undergo biopsy or resection to obtain tumor for generation of autologous TIL cultures and autologous cancer cell lines.
* All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine.
* On day 0 patients will receive between 1x10\^9 to 2x10\^11 young TIL and then begin high dose aldesleukin (720,000 IU/kg intravenous (IV) every 8 hours for up to 15 doses) or no aldesleukin if they are not medically eligible to receive it.
* A complete evaluation of evaluable lesions will be conducted 4-6 weeks after the last dose of aldesleukin in the aldesleukin arm and 4-6 weeks after the cell administration in the no aldesleukin arm.
* Patients will be enrolled into two cohorts. The cohort receiving high-dose aldesleukin (cohort A) will be conducted using a small optimal two-stage Phase II design, initially 19 patients will be enrolled, and if 4 or more of the first 19 patients have a clinical response (partial response (PR) or complete response (CR), accrual will continue to 33 patients, targeting a 35% goal for objective response. For the cohort that will not receive aldesleukin (cohort B), the study will be conducted as a Minimax two-stage phase II trial. Initially 12 evaluable patients will be enrolled to this cohort, and if 1 or more the first 12 have a response, then accrual would continue until a total of 21 patients, targeting a 20% goal for objective response.
