Chemotherapy Followed by ESO-1 Lymphocytes and Aldesleukin to Treat Metastatic Cancer
Condition: Metastatic Melanoma; Metastatic Renal Cell Cancer; Metastatic Cancer
MeSH terms: Melanoma; Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary; Carcinoma, Renal Cell
Intervention: Anti-NY ESO-1 T-cell receptor PBL; aldesleukin; Cyclophosphamide; fludarabine phosphate; ALVAC NY ESO-1 vaccine
Intervention description: Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.; Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses); Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.; Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.; Approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10e7 cell culture infectious dose 50 (CCID50) (with a range of approximately 10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 66 Years
Healthy volunteers: No
Keywords: Metastatic Cancer; Gene Therapy; Immunotherapy; Tumor Regression; Metastatic Melanoma; Metastatic Renal Cell Cancer

Summary:

      Background:

      -This study uses an experimental cancer treatment that uses the patient s own lymphocytes
      (type of white blood cell), which are specially selected and genetically modified to target
      and destroy their tumor.

      Objectives:

      -To test the safety of the treatment and determine if it can cause the patient s tumor to
      shrink.

      Eligibility:

        -  Patients greater than 18 years and less than or equal to 66 years of age whose cancer
           has spread beyond the original site and does not respond to standard treatment.

        -  Patients have tissue type human leukocyte antigen (HLA)-A*0201.

        -  Patients cancer cells have the ESO-1 gene.

      Design:

        -  Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.

        -  Patients have leukapheresis to collect cells for laboratory treatment and later
           reinfusion. For this procedure, whole blood is collected thorough a tube in a vein, the
           desired cells are extracted from the blood, and the rest of the blood is returned to the
           patient.

        -  Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune
           system to receive the treated lymphocytes.

        -  Cell infusion and aldesleukin (IL-2) treatment: Patients receive the lymphocytes by a
           30-minute infusion through a vein. Starting within 24 hours of the infusion, they
           receive high-dose aldesleukin infusions every 8 hours for up to 5 days (maximum15
           doses).

        -  Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and
           aldesleukin.

        -  Tumor biopsy: Patients may be asked to undergo a biopsy (surgical removal of a small
           piece of tumor) after treatment to look at the effects of treatment on the immune cells
           in the tumor.

        -  Follow-up: After treatment is completed, patients return to the clinic once a month for
           several months for physical examinations, a review of side effects, laboratory tests and
           scans. They may undergo leukapheresis at some visits to look at the effect of treatment
           on the immune system and check the viability of the infused cells. Patients then return
           to the National Institute of Health (NIH) clinic once a year for 5 years and then
           complete a follow-up questionnaire for another 10 years.

        -  Retreatment: Patients whose tumor shrinks or disappears following treatment and then
           recurs may receive one additional treatment, using the same regimen of chemotherapy,
           lymphocyte infusion and IL-2 treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Metastatic cancer that expresses ESO as assessed by one of the following methods:
             reverse transcription-polymerase chain reaction (RT-PCR) on tumor tissue, or by
             immunohistochemistry of resected tissue, or serum antibody reactive with ESO.
             Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the
             National Cancer Institute (NCI).

          -  Patients with histologies other than metastatic melanoma, must have previously
             received systemic standard care (or effective salvage chemotherapy regimens) for
             metastatic disease, if known to be effective for that disease, and have been either
             non-responders (progressive disease) or have recurred.

          -  Greater than or equal to 18 years of age. and less than or equal to 66 years of age.

          -  Willing to sign a durable power of attorney.

          -  Able to understand and sign the Informed Consent Document.

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

          -  Life expectancy of greater than three months.

          -  Patients of both genders must be willing to practice birth control for four months
             after receiving the preparative regimen.

          -  Patients must be human leukocyte antigen (HLA)-A*0201 positive

          -  Serology:

               -  Seronegative 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.)

               -  Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen
                  negative. If hepatitis C antibody test is positive, then patients must be tested
                  for the presence of antigen by RT-PCR and be hepatitis C virus ribonucleic acid
                  (HCV RNA) negative.

          -  Hematology:

               -  Absolute neutrophil count greater than 1000/mm(3) without the support of
                  filgrastim.

               -  White blood cell (WBC) (greater than 3000/mm(3)).

               -  Platelet count greater than 100,000/mm(3).

               -  Hemoglobin greater than 8.0 g/dl.

          -  Chemistry:

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or
                  equal to 2.5 times the upper limit of normal.

               -  Serum creatinine less than or equal to 1.6 mg/dl.

               -  Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilberts
                  Syndrome who must have a total bilirubin less than 3.0 mg/dl.

          -  More than four weeks must have elapsed since any prior systemic therapy at the time
             the patient receives the preparative regimen, and patients toxicities must have
             recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

          -  Six weeks must have elapsed since prior ipilimumab therapy to allow antibody levels to
             decline.

          -  Patients who have previously received ipilimumab or ticilimumab anti-programmed cell
             death protein 1 (PD1) or anti-PD-L1 antibodies, and have documented gastrointestinal
             (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

        EXCLUSION CRITERIA:

          -  Prior vaccination with an replication-defective recombinant canarypox virus (ALVAC)
             containing vaccine for patients who will receive the ALVAC ESO-1 vaccine (cohorts 3 or
             4).

          -  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.

          -  Active systemic infections, coagulation disorders or other major medical illnesses of
             the cardiovascular, respiratory or immune system, myocardial infarction, cardiac
             arrhythmias, obstructive or restrictive pulmonary disease.

          -  Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
             Disease).

          -  Concurrent 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).

          -  Concurrent Systemic steroid therapy.

          -  Known systemic hypersensitivity to any of the vaccine components, including egg
             products or Neomycin for patients who will receive the ALVAC ESO-1 vaccine (cohorts 3
             or 4).

          -  History of severe immediate hypersensitivity reaction to any of the agents used in
             this study.

          -  History of coronary revascularization or ischemic symptoms.

          -  Any patient known to have an left ventricular ejection fraction (LVEF) less than or
             equal to 45 percent.

          -  Documented forced expiratory volume (LVEF) of less than or equal to 45 percent tested
             in patients with:

               -  History of ischemic heart disease, chest pain, or clinically significant atrial
                  and/or ventricular arrhythmias including but not limited to: atrial fibrillation,
                  ventricular tachycardia, second or third degree heart block.

               -  Age greater than or equal to 60 years old.

          -  Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60
             percent predicted tested in patients with:

               -  A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2
                  years).

               -  Symptoms of respiratory dysfunction