Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV 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

   - Confirmed IL13Ralpha2 tumor expression by immunohistochemistry (>= 20%, 1+)

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

   - A minimum of one measurable lesion defined as:

      - Meeting the criteria for measurable disease according to Response Evaluation
      Criteria in Solid Tumors (RECIST), OR

      - 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)

   - Absolute neutrophil count (ANC) >= 1 x 10^9 cells/L (determined within 30?60 days
   prior to enrollment; re-evaluated within 14 days of beginning conditioning
   chemotherapy)

   - Platelets >= 75 x 10^9/L (determined within 30?60 days prior to enrollment;
   re-evaluated within 14 days of beginning conditioning chemotherapy)

   - Hemoglobin >= 8 g/dL (determined within 30?60 days prior to enrollment; re-evaluated
   within 14 days of beginning conditioning chemotherapy)

   - Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal
   (ULN) (determined within 30?60 days prior to enrollment; re-evaluated within 14 days
   of beginning conditioning chemotherapy)

   - Total bilirubin =< 2 x ULN (except patients with documented Gilbert?s syndrome)
   (determined within 30?60 days prior to enrollment; re-evaluated within 14 days of
   beginning conditioning chemotherapy)

   - Creatinine < 2 mg/dL (or a glomerular filtration rate > 45) (determined within 30?60
   days prior to enrollment; re-evaluated within 14 days of beginning conditioning
   chemotherapy)

   - Must have received at least one prior systemic therapy for advanced melanoma (i.e.
   anti-PD-1 therapy, BRAF plus MEK inhibitor therapy for BRAFV600 mutated melanoma) and
   is not considered to have an alternate treatment option with curative intent

   - Must be willing and able to accept at least one leukapheresis procedure

   - Must be willing and able to provide written informed consent

Exclusion Criteria:

   - Inability to purify >= 1 x 10^7 T cells from leukapheresis product

   - Previously known hypersensitivity to any of the agents used in this study; known
   sensitivity to cyclophosphamide or fludarabine

   - Received systemic treatment for cancer, including immunotherapy, within 14 days prior
   to initiation of conditioning chemotherapy administration within this protocol

   - Potential requirement for systemic corticosteroids or concurrent immunosuppressive
   drugs based on prior history or received systemic steroids within the last 2 weeks
   prior to enrollment (inhaled or topical steroids at standard doses are allowed)

   - Human immunodeficiency virus (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 with evidence of ongoing liver damage, which would
   increase the likelihood of hepatic toxicities from the chemotherapy conditioning
   regimen and supportive treatments. 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

   - Dementia or significantly altered mental status that would prohibit the understanding
   or rendering of informed consent and compliance with the requirements of this protocol

   - A Tiffeneau-Pinelli index < 70% of the predicted value. Subjects will be excluded if
   pulmonary function tests indicate they have insufficient pulmonary capability

   - Patients will be excluded if they have a history of clinically significant
   electrocardiography (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias
   and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test
   (stress thallium, stress multigated acquisition scan (MUGA), dobutamine
   echocardiogram, or other stress test)

   - Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT
   (QTC) > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus
   tachycardia (HR>120 beats per minute) will be evaluated by a cardiologist prior to
   starting the trial. Patients with any arrhythmias, including atrial
   fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular
   complex [PVC]s per minute), ventricular tachycardia, 3rd degree heart block will be
   excluded from the study unless cleared by a cardiologist

   - Pregnancy or breast-feeding. Female patients must be surgically sterile or be
   postmenopausal for two years, or must agree to use effective contraception during the
   period of treatment and for 6 months afterwards. All female patients with reproductive
   potential must have a negative pregnancy test (serum/urine) at screening and again
   within 14 days from starting the conditioning chemotherapy. The definition of
   effective contraception will be based on the judgment of the study investigators.
   Patients who are breastfeeding are not allowed on this study

   - A concomitant active malignancy that would be considered to interfere with the
   assessment of the primary or secondary endpoints of the study