Inclusion Criteria:

- Step I

Inclusion Criteria:

- Stage III-IV melanoma that is unlikely to be cured by surgery

- Able to tolerate high-dose cyclophosphamide, fludarabine and high-dose IL-2

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Patients must have a magnetic resonance imaging (MRI), computed tomography (CT),
or positron emission tomography (PET) of the brain within 2 months before
consenting. If new lesions are present, principal investigator (PI) or designee
should make final determination regarding enrollment

- Patients must have a site of metastatic disease that can be safely resected or
biopsied for tissue sufficient for tumor-infiltrating lymphocyte (TIL) harvest

- A stress cardiac test (e.g., stress treadmill, stress thallium, stress multi
gated acquisition scan [MUGA], dobutamine echocardiogram) to rule out cardiac
ischemia within 4 months before Step I is required for all patients with
underlying risk factors such as diabetes or hypertension, or who have a history
of cardiac disease

- Step II

Inclusion Criteria:

- Patients must have measurable metastatic melanoma

- Able to tolerate high-dose cyclophosphamide, fludarabine, and high-dose IL-2

- ECOG performance status of 0-1 at time of lymphodepletion

- Patients must have brain imaging by MRI, CT or PET within 30 days prior to
lymphodepletion; patients may have up to 2 asymptomatic brain lesions < 1cm
each; 1-3 lesions that are >1cm that have been irradiated and in the opinion of
the investigator no longer represents active disease will also be allowed

- A stress cardiac test (e.g., stress treadmill, stress thallium, stress MUGA,
dobutamine echocardiogram) to rule out cardiac ischemia within 4 months prior to
lymphodepletion is required for all patients

- PFTs are required of all patients within 4 months prior to lymphodepletion; FEV1
and FVC must be >= 65% predicted and DLCO must be >= 50% predicted

- Patients must have adequate TIL (at least 40 x 10^6 cells at the pre-expansion
stage)

Exclusion Criteria:

- Step I Exclusion Criteria:

- Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception or abstinence for 4 months after
treatment

- Calculated creatinine clearance (estimated glomerular filtration rate [eGFR]) <
60ml/min

- Significant hepatic dysfunction (aspartate aminotransferase [AST]/alanine
aminotransferase [ALT] > 3 x upper limit of normal

- Total bilirubin > 2.0 mg/dl, except in patients with Gilbert's Syndrome whose
total bilirubin must not exceed 3.0 mg/dl) deemed by investigator to be
irreversible

- Forced expiratory volume in 1 second [FEV1] < 65% predicted, forced vital
capacity (FVC) < 65% of predicted, diffusing capacity of lung for carbon
monoxide (DLCO) (corrected for hemoglobin [Hgb]) < 50% predicted); pulmonary
function tests (PFTs) within 4 months prior to consent for Step I will be
required for patients with underlying risk factors such as smoking history, or
history of lung disease

- Significant cardiovascular abnormalities as defined by any one of the following:

- Congestive heart failure,

- Clinically significant hypotension, cardiac ischemia, or symptoms of
coronary artery disease,

- Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug
therapy,

- Ejection fraction < 45% (echocardiogram or MUGA), although any patient with
an ejection fraction between 45-49% must receive clearance by a
cardiologist to be eligible for this trial

- Clinically significant autoimmune disorders or conditions of immunosuppression;
patients with acquired immunodeficiency syndrome (AIDS) or human
immunodeficiency virus (HIV)-1 associated complex or known to be HIV antibody
seropositive or known to be recently polymerase chain reaction (PCR)+ for
hepatitis B or C are not eligible for this study; the severely depressed or
altered immune system found in these patients and the possibility of premature
death would compromise study objectives

- Patients with active systemic infection requiring intravenous antibiotics

- Clinically significant psychiatric disease which, in the opinion of the PI or
sub-I, would render immunotherapy and its potential sequelae unsafe or
compliance with procedural requirements unlikely

- Step II Exclusion Criteria:

- Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception or abstinence; women of childbearing
potential must have a negative pregnancy test within 7 days prior to entry;
patients of both genders must practice birth control during treatment and for
four months after treatment

- Calculated creatinine clearance (eGFR) < 60ml/min

- AST/ALT > 3 x upper limit of normal

- Total bilirubin > 2.0 mg/dl, except in patients with Gilbert's Syndrome whose
total bilirubin must not exceed 3.0 mg/dl)

- Clinically significant pulmonary dysfunction (FEV1< 65% predicted or FVC < 65%
of predicted, DLCO (corrected for Hgb) < 50% predicted)

- Significant cardiovascular abnormalities as defined by any one of the following:

- Congestive heart failure,

- Clinically significant hypotension,

- Cardiac ischemia, or symptoms of coronary artery disease,

- Presence of cardiac arrhythmias on EKG requiring drug therapy,

- Ejection fraction < 45% (echocardiogram or MUGA), although any patient with
an ejection fraction between 45-49% must receive clearance by a
cardiologist to be eligible for this trial

- Absolute neutrophil count less than 1000/mm^3

- Platelet count less than 100,000/mm^3

- Hemoglobin less than 10.0g/dl

- Untreated central nervous system metastases that are either symptomatic or
greater than 1 cm at time of therapy; 1-3 lesions that are > 1cm that have been
treated with stereotactic radiosurgery (SRS) and in the opinion of the PI or
sub-I no longer represent active disease may be allowed

- Patients with systemic infections requiring active therapy within 72 hours of
lymphodepletion

- Systemic cancer therapy (standard or experimental), including cytotoxic
chemotherapy or IL-2, received less than 4 weeks or checkpoint blocking agents
(e.g., CTLA-4 or PD1/PD-L1 inhibitors) received less than 6 weeks prior to
lymphodepletion, with the exception of targeted therapies

- Commercially available, molecularly targeted therapies (e.g., vemurafenib,
imatinib) taken within 7 days prior to lymphodepletion

- Clinically significant autoimmune disorders or conditions of immunosuppression;
patients with AIDS or HIV-1 associated complex or known to HIV antibody
seropositive or known to be recently PCR+ for hepatitis B or C virus are not
eligible for this study; virology testing will be done within 6 months of T cell
infusion; the severely depressed or altered immune system found in these
patients and the possibility of premature death would compromise study
objectives

- Prior treatment with systemic steroids within 4 weeks prior to lymphodepletion
(except for physiologic replacement doses for adrenal insufficiency) or topical
steroids within 2 weeks prior to lymphodepletion

- Any other significant medical or psychological conditions that would make the
patient unsuitable candidate for cell therapy at the discretion of the PI