Laboratory-Treated Autologous Lymphocytes and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Intervention: Tumor Infiltrating Lymphocytes (TIL)
Intervention description: Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV melanoma; recurrent melanoma

Summary:

      RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor
      cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill
      tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Giving laboratory-treated lymphocytes and aldesleukin together with
      cyclophosphamide and fludarabine may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes
      and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients
      with metastatic melanoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of metastatic melanoma

          -  Refractory to standard treatment including high-dose aldesleukin (IL-2), unless
             previously ineligible for or refused IL-2

          -  Measurable disease with ≥ 1 lesion that is resectable for tumor-infiltrating
             lymphocyte generation

          -  Patients with ≥ 1 brain metastases < 1 cm each, or 1-2 brain metastases > 1 cm are
             eligible provided they have been treated and stable for ≥ 3 months

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  Life expectancy > 3 months

          -  ANC > 1,000/mm^3 (without filgrastim support)

          -  WBC > 3,000/mm^3

          -  Hemoglobin > 8.0 g/dL

          -  Platelet count > 100,000/mm^3

          -  Serum ALT/AST < 3 times upper limit of normal

          -  Total bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)

          -  Serum creatinine ≤ 1.6 mg/dL

          -  LVEF > 45% in patients meeting the following criteria:

               -  Clinically significant atrial and/or ventricular arrhythmias, including, but not
                  limited to, atrial fibrillation, ventricular tachycardia, or second- or
                  third-degree heart block

               -  At least 60 years of age

          -  FEV_1 > 60% in patients meeting the following criteria:

               -  Prolonged history of cigarette smoking

               -  Symptoms of respiratory dysfunction

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 4 months after
             completion of study treatment

          -  No HIV or hepatitis B or C positivity

          -  No form of primary immunodeficiency (e.g., severe combined immunodeficiency disease or
             AIDS)

          -  No opportunistic infections

          -  No active systemic infections

          -  No history of severe immediate hypersensitivity reaction to any of the agents used in
             this study

          -  No coagulation disorders

          -  No myocardial infarction, cardiac arrhythmias, or positive stress thallium or
             comparable test

          -  No history of coronary revascularization or ischemic symptoms

          -  No obstructive or restrictive pulmonary disease

          -  No other active major medical illness of the cardiovascular, respiratory, or immune
             system

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from prior therapy (alopecia or vitiligo allowed)

          -  At least 6 weeks since prior ipilimumab

               -  Must have normal colonoscopy with normal colonic biopsies

          -  At least 4 weeks since prior systemic therapy

          -  Minor surgical procedures within the past 3 weeks allowed provided all toxicities have
             recovered to ≤ grade 1

          -  No concurrent systemic steroids

          -  No other concurrent experimental agents