A Study Using Tumor-Reactive Autologous Tumor Infiltrating Lymphocytes (TIL) in Metastatic Melanomas
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Tumor Infiltrating Lymphocytes (TIL)
Intervention description: Patients will receive an IV adoptive transfer of at least 10^9 tumor-reactive lymphocytes. An IV catheter in the patient's arm or upper chest will be used for cell infusion. The TIL will be administered over 20-30 minutes at room temperature using a standard infusion protocol or by hanging the infusion bag from a stand and allowing gravity to pull the cells down.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this protocol is to determine whether autologous TIL infused in conjunction
      with systemic high-dose IL-2 after non-myeloablative chemotherapy with cyclophosphamide and
      fludarabine can cause consistent and durable objective responses in patients who have
      metastatic melanoma at the John Wayne Cancer Institute (JWCI).
    

Eligibility criteria:

        Inclusion Criteria -

          -  Patients must have metastatic melanoma with a resectable metastatic lesion of
             sufficient size and be willing to undergo such a resection for experimental purposes.

          -  Patients must be > 18 years of age.

          -  Patients must have measurable disease measured by Response Evaluation Criteria in
             Solid Tumors (RECIST) 1.1 criteria (in addition to the resected lesion).

          -  Patients of child bearing potential must agree to use an effective form of birth
             control during study and up to four months after receiving treatment.

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1.

          -  Absolute neutrophil count greater than 1000/mm3 without support of filgrastim.

          -  Platelet count greater than 100,000/mm3.

          -  Serum Alanine transaminase/Aspartate transaminase (ALT/AST) less than three times the
             upper limit of normal.

          -  Serum creatinine less than or equal to 1.6 mg/dl.

          -  Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's
             Syndrome who must have a total bilirubin less than 3 mg/dl.

          -  Patients must be able to understand and sign the Informed Consent document.

        Exclusion Criteria - Tumor/TIL Harvest Exclusion Criteria

          -  All systemic, cytotoxic therapy (including targeted therapies) must be stopped at
             least 5 weeks prior to cell infusion (see 2.1.3).

          -  Women who are pregnant or breastfeeding.

          -  Life expectancy of less than three months.

          -  Patients who have received prior treatment with anti-cytotoxic T lymphocyte-associated
             antigen 4 (anti-CTLA-4) antibody will be excluded unless a post anti-CTLA-4 antibody
             treatment colonoscopy was normal with normal colonic biopsies.

          -  Patients who require immediate active treatment for symptomatic Central Nervous System
             (CNS) lesions will not be eligible until after treatment of their symptomatic lesions.

        Cell Infusion Exclusion Criteria

          -  Less than 5 weeks has elapsed since any prior systemic therapy at the time the patient
             receives the preparative regimen. All patients' toxicities must have recovered to a
             grade 1 or less or as specified in the eligibility criteria in Section 2.1.1. Patients
             may have undergone minor surgical procedures or focal palliative radiotherapy (to
             non-target lesions) within the past 5 weeks, as long as all toxicities have recovered
             to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1.

          -  Women of child-bearing potential who are pregnant or breastfeeding.

          -  Life expectancy of less than three months.

          -  Systemic steroid therapy more than the equivalent of 10mg/day of prednisone.

          -  Hemoglobin less than 8g/dl unable to be corrected with transfusion.

          -  Any active systemic infections, coagulation disorders or other active major medical
             illnesses of the cardiovascular, respiratory or immune system, as evidenced by a
             positive stress thallium or comparable test, myocardial infarction, cardiac
             arrhythmias, obstructive or restrictive pulmonary disease.

          -  Any form of primary or secondary immunodeficiency. Must have recovered immune
             competence after chemotherapy or radiation therapy as evidenced by normal Absolute
             Neutrophil Count (ANC) > 1000/mm3 and absence of opportunistic infections. (The
             experimental treatment being evaluated in this protocol depends on an intact immune
             system. Patients who have decreased immune competence may be less responsive to the
             experimental treatment and more susceptible to its toxicities.)

          -  Seropositive for HIV antibody.

          -  Patients with active hepatitis B or active hepatitis C.

          -  The following patients will be excluded because of inability to receive high dose
             proleukin:

          -  Patients will be excluded if they have a history of major EKG abnormalities, symptoms
             of cardiac ischemia or arrhythmias and have a Left Ventricular Ejection Fraction
             (LVEF) < 45% on a cardiac stress test (stress thallium, stress Multi Gated Acquisition
             Scan (MUGA), dobutamine, echocardiogram or other stress test)

          -  Patients who have a prolonged history of cigarette smoking or symptoms of respiratory
             dysfunction will be excluded if they have an abnormal pulmonary function test as
             evidenced by a Forced Expiratory Volume at one second Forced Expiratory Volume at one
             second (FEV1)< 60% predicted.

          -  Patients who have received prior treatment with anti-CTLA-4 antibody will be excluded
             unless a subsequent colonoscopy was normal with normal colonic biopsies (to rule out
             colitis).

          -  Patients who require immediate treatment for symptomatic CNS lesions will not be
             eligible until after treatment of their symptomatic lesions and resolution of
             symptoms.