Natural Killer Cells Plus IL-2 Following Chemotherapy to Treat Advanced Melanoma or Kidney Cancer
Condition: Metastatic Melanoma; Metastatic Kidney Cancer
MeSH terms: Melanoma; Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: Natural Killer (NK) Lymphocytes; IL-2; Cyclophosphamide; Fludarabine
Intervention description: Thirty minutes infusion of natural killer (NK) cells 2 days after last dose of chemotherapy.; IL-2 720,000 IU/kg/intravenous every 8 hours for up to 5 days.; Cyclophosphamide 60 mg/kg/day intravenous on days -8 and -7.; Fludarabine 25 mg/m^2 day intravenous on days -6 through -2.
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adoptive Cell Therapy; Cutaneous Melanoma; Clinical Response; Rate of Repopulation; Toxicity Profile; Metastatic Melanoma; Metastatic Kidney Cancer

Summary:

      Background:

        -  Natural killer (NK) cells are large lymphocytes (a type of white blood cell) that are
           important in the immune response to cancer.

        -  IL-2 (Aldesleukin) is a substance the body makes that controls the growth and function
           of many types of cells. The Food and Drug Administration has approved IL-3 for treating
           metastatic melanoma and kidney cancer. (Metastatic disease is cancer that has spread
           beyond the primary site.)

      Objectives: To determine the safety and effectiveness of treating metastatic melanoma and
      kidney cancer with laboratory-treated NK cells and IL-2.

      Eligibility: Patients 18 years of age or older with metastatic melanoma or kidney cancer who
      have previously been treated with high-dose IL-2.

      Design:

        -  Leukapheresis. Patients under leukapheresis to obtain NK cells for the treatment
           regimen. Blood is collected through a needle in an arm vein and directed through a cell
           separator machine where white blood cells are extracted. The rest of the blood is
           returned to the patient through a needle in the other arm. NK cells are removed from the
           white blood cells and treated for re-infusion into the patient.

        -  Chemotherapy. Starting 8 days before infusion of the treated NK cells, patients receive
           intravenous (IV, through a vein) infusions of cyclophosphamide and fludarabine to
           suppress the immune system.

        -  NK cell infusion. Patients receive a 30-minute IV infusion of NK cells 2 days after the
           last dose of chemotherapy.

        -  IL-2 therapy. Within 24 hours of the NK cell infusion, patients receive high-dose IL-2
           as a 15-minute IV infusion every 8 hours for up to 5 days. A second cycle of IL-2 is
           given about 14 days after the first.

        -  Blood tests and biopsy. Patients have frequent blood tests during the treatment period
           and may be asked to undergo a biopsy (surgical removal of a small piece of tumor or
           lymph node) at the end of treatment to look at the effects of the treatment on the tumor
           immune cells.

        -  Follow-up evaluation. Patients are evaluated 4-6 weeks after completing treatment. They
           have a physical examination, scans of tumor sites, blood tests and blood sampling (or
           leukapheresis) to examine the response to treatment. Patients who improve with treatment
           return for evaluations every month. Those whose tumor grows again after originally
           shrinking may receive one additional treatment course.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Patients must have previously received high dose IL-2 (aldesleukin) and have been
                  either non-responders (progressive disease) or have recurred.

               2. Patients who are greater than or equal to 18 years of age, must have measurable
                  metastatic melanoma or metastatic kidney cancer and no tumor reactive T cells
                  available for cell transfer therapy.

               3. Pathology for metastatic melanoma or metastatic kidney cancer to be confirmed by
                  the National Cancer Institute (NCI) Laboratory of Pathology.

               4. Patients of both genders must be willing to practice birth control for four
                  months after receiving the preparative regimen.

               5. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1.

               6. Absolute neutrophil count greater than 1000/mm^3.

               7. Platelet count greater than 100,000/mm^3.

               8. Hemoglobin greater than 8.0 g/dl.

               9. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than
                  three times the upper limit of normal.

              10. Serum creatinine less than or equal to 1.6 mg/dl.

              11. Total bilirubin less than or equal to 2.0 mg/dl, except in patients with
                  Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

              12. Must be willing to sign a durable power of attorney.

        EXCLUSION CRITERIA:

          1. Less than four weeks has elapsed since any prior systemic therapy at the time the
             patient receives the preparative regimen, or less than six weeks since prior
             nitrosurea therapy.

          2. Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

          3. Life expectancy of less than three months.

          4. Systemic steroid therapy required.

          5. Any active systemic infections, coagulation disorders or other 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.

          6. Any form of autoimmune disease (such as autoimmune colitis or Crohn's Disease).

          7. Seropositive for human immunodeficiency virus (HIV) antibody. (The experimental
             treatment being evaluated in this protocol depends on an intact immune system.
             Patients who are HIV seropositive can have decreased immune competence and thus be
             less responsive to the experimental treatment and more susceptible to its toxicities.)

          8. Seropositive for hepatitis B or C antigen.

          9. Seronegative for Epstein-Barr virus (EBV).

         10. Patients who are not eligible to receive high-dose Aldesleukin as evaluated by the
             following:

               1. Patients who are 50 years old or greater who do not have a normal stress cardiac
                  test (stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine
                  echocardiogram, or other stress test) will be excluded.

               2. Patients who have history of electrocardiogram (EKG) abnormalities, symptoms of
                  cardiac ischemia or arrhythmias who do not have a normal stress cardiac test
                  (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test)
                  will be excluded.

               3. Patients with a prolonged history of cigarette smoking or symptoms of respiratory
                  dysfunction who do not have a normal pulmonary function test as evidenced by a
                  forced expiratory volume 1 (FEV1) less than 60% predicted will be excluded.

               4. Patients who experienced toxicities during prior IL-2 administration that would
                  preclude redosing with IL-2, i.e. myocardial infarction, mental status changes
                  requiring intubation, bowel perforation or renal failure requiring dialysis.