Pembrolizumab, Standard Chemotherapy, Tumor Infiltrating Lymphocytes, and High- or Low-Dose Aldesleukin in Treating Patients With Metastatic Melanoma

TURNSTILE I - SCREENING:

Patients must have metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease

Patients must have a lesion amenable to resection for the generation of TIL on MD Anderson protocol 2004-0069

Patients must receive a magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) of the brain within 6 months of signing informed consent; if new central nervous system (CNS) lesions are present, patient must have definitive treatment (including surgery or radiation); principal investigator (PI) or his designee should make final determination regarding enrollment

Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1 within 30 days of signing informed consent

Patients previously treated with immunotherapy, targeted therapy, or no therapy (treatment naive) will be eligible

Patients receiving cytotoxic agents will be evaluated by the PI or his designee for eligibility suitability

Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP); a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not had menses at any time in the preceding 12 consecutive months)

TURNSTILE II - TREATMENT:

Patients must sign the treatment consent document before Turnstile II screening procedures; before the treatment starts and at each visit, the patient will be asked to complete two quality of life questionnaires; It should take about 15 minutes to complete the questionnaires (Functional Assessment of Cancer Therapy General \[FACT-G\], FACT-Melanoma); patients must fulfill all of the following criteria to be eligible for Turnstile II of the study

Patients must have adequate TIL that were previously harvested and then cryopreserved on MD Anderson Cancer Center (MDACC) protocol 2004-0069

Patients who have had prior therapy (BRAF inhibitors, ipilimumab, anti PD-1 antibody or anti PD-L1 antibody) or treatment naive patients are eligible as long as toxicity from therapy is grade =\< 1 or at baseline

Patients must have at least one biopsiable measurable metastatic melanoma, lesion \> 1 cm and must be amenable to undergoing serial biopsies through the course of therapy; this lesion must not be documented as one of the target lesions

Patients may have central nervous system (CNS) metastases which have been treated and are radiographically stable for at least 4 weeks

Patients of both genders must practice birth control for four months after receiving the preparative regimen (lymphodepletion) and continue to practice birth control throughout the study; patients must have a documented negative pregnancy test (urine or serum) for women who have menstruated in the past 12 months and without sterilization surgery

Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), or if the patient is post-menopausal, the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, intrauterine device (IUD), or sponge plus spermicide; abstinence is an acceptable form of birth control

Pregnancy testing will be performed within 14 days of screening for women of childbearing potential (WOCBP); a WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not had menses at any time in the preceding 12 consecutive months)

Clinical performance status of ECOG 0-1 within 30 days of signing informed consent

A stress cardiac test (stress thallium, stress multi-gated acquisition scan \[MUGA\], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) within 1 month of lymphodepletion

12-lead electrocardiogram (EKG) showing no active ischemia and corrected QT (QTc) interval less than 480 msec

Pulmonary function tests (forced expiratory volume in 1 second \[FEV1\] \> 65% or forced vital capacity \[FVC\] \> 65% of predicted) within 1 month of lymphodepletion

Have measurable disease based on RECIST 1.1 and immune related response (irRC) criteria

Absolute neutrophil count (ANC) \>= 1,500 /mcL (within 10 days of treatment initiation)

Platelets \>= 100,000 /mcL (within 10 days of treatment initiation)

Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 10 days of treatment initiation)

Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 X upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (within 10 days of treatment initiation)

Serum total bilirubin =\< 1.5 X ULN (within 10 days of treatment initiation) OR

Direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (within 10 days of treatment initiation)

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN or =\< 5 X ULN for subjects with liver metastases (within 10 days of treatment initiation)

International normalized ratio (INR) or prothrombin time (PT)/activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

What this study is about