Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

Inclusion Criteria

Step I Inclusion Criteria:

• Stage IV melanoma or stage III 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 known history of brain metastasis or if clinically indicated; 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 TIL harvest

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
• Patients must have brain imaging by MRI, CT or PET within 30 days prior to lymphodepletion; patients may have asymptomatic brain lesions that are = 1 cm that have been irradiated and in the opinion of the investigator no longer represents active disease will also be allowed
• A functional cardiac test (e.g., stress treadmill, stress thallium, multigated acquisition scan (MUGA), dobutamine echocardiogram) to rule out cardiac ischemia within 4 months prior to lymphodepletion is required for all patients
• Pulmonary function tests (PFTs) are required of all patients within 4 months prior to lymphodepletion; forced expiratory volume (FEV)1 and forced vital capacity (FVC) must be >= 65% predicted and diffusion lung capacity for carbon monoxide (DLCO) must be >= 50% predicted
• Patients must have their tumor sent for v-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutational analysis
• Patients must have adequate TIL (at least 40 x 10^6 cells at the pre-expansion stage)

Exclusion Criteria

Step I Exclusion Criteria:

• 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]) 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
• FEV1 10 pack years, or a history of pre-existing symptomatic lung disease (not including melanoma metastases to the lung)
• Pre-existing known 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 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 1cm that have been irradiated 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., cytotoxic T-lymphocyte protein [CTLA]-4 or programmed cell death protein [PD]1/PD-ligand [L]1 inhibitors) received less than 6 weeks prior to lymphodepletion, with the exception of targeted therapies
• Commercially available, molecularly targeted therapies (e.g., dabrafenib, trametinib, 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 el