Study of Gene Modified Immune Cells in Patients With Advanced Melanoma

Inclusion Criteria

• Histologically confirmed melanoma that is considered surgically incurable with either:
• Stage IIIc melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis.
• Stage IV melanoma (M1a, M1b or M1c). At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists. Patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion.
• MART-1 positive melanoma by RT-PCR or Immuno-histochemical (IHC).
• HLA-A*0201 (HLA-A2.1) positivity by molecular subtyping*.
• Age greater than or equal to 18 years old.
• Life expectancy greater than 3 months assessed by a study physician.
• A minimum of one measurable lesion defined as:
• Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST).
• Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s).
• No restriction based on prior treatments.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
• Adequate bone marrow and hepatic function determined within 30-60 days prior to enrollment, defined as:
• Absolute neutrophil count >= 1.5 x 109 cells/L.
• Platelets >= 100 x 109/L.
• Hemoglobin >= 10 g/dL.
• Aspartate and alanine aminotransferases (AST, ALT) = 60).
• Must be willing and able to accept at least two leukapheresis procedures.
• Must be willing and able to accept at least two tumor biopsies.
• Must be willing and able to provide written informed consent.
• Patients with HLA-A*0205 (HLA-A2.5) positivity by molecular subtyping may be eligible if there is demonstration that they can correctly present the MART-126-35 epitope as stimulators for IFN-gamma production by MART-1 F5 TCR transgenic cells.

Exclusion Criteria

• Previously known hypersensitivity to any of the agents used in this study.
• Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol. However, cell harvesting by leukapheresis may be performed before one month from prior therapy if the study investigators consider that it will not have a detrimental impact on the generation of the two cell therapies in this protocol.
• History of, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.). Patients will be eligible if prior autoimmune disease is not deemed to be active (e.g. fibrotic damage of the thyroid after thyroiditis or its treatment, with stable thyroid hormone replacement therapy). Vitiligo will not be a basis for exclusion.
• History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin.
• Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed).
• HIV seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist.
• Hepatitis B or C seropositivity w