Lymphocyte Re-infusion During Immune Suppression to Treat Metastatic Melanoma
Condition: Melanoma; Neoplasm Metastasis
MeSH terms: Melanoma; Neoplasm Metastasis
Intervention: gp100:209-217 (210M); Montanide ISA-51; IL-2; MART-1:26-35(27L); Abl cells; Fludarabine; Cyclophosphamide; GCSF (Growth colony stimulating factor); Apheresis
Intervention description: gp100 = gp100:209-217(210M) peptide - 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus gp100:209-217(210M) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.
MART-1 = MART-1:26-35(27L) peptide- 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus MART-1:26-35(27L) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.; MART-1 = MART-1:26-35(27L) peptide- 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus MART-1:26-35(27L) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.; 125,000 IU/kg dose intravenous for 5 days for 6 weeks with 2 days rest per week.
720,000 IU/kg intravenous every 8 hours for a maximum of 12 doses.; MART-1 = MART-1:26-35(27L) peptide- 1 mg in IFA SQ (in the subcutaneous tissue of each thigh) on the morning of the cell infusion, plus MART-1:26-35(27L) peptide, 1 mg, in IFA injected into the subcutaneous tissue in two equal volumes, 1.0 mL for each injection, within 2cm of each other, in the thigh daily for five days starting on the morning of the cell infusion and then weekly for 3 more injections.; Abl cells IV = Lymphocytes 10^9-10^11 IV over 30 minutes on day 0, repeated in 14 to 21 days Abl cells IA = Lymphocytes 10^9-10^11 IA over 30 minutes on day 0, repeated in 14 to 21 days; 5x25 mg/m^2 intravenous; 2x30 mg/kg, 2x60 mg/kg intravenous; Beginning on day 1 or 2, GCSF will be administered subcutaneously at a dose of 5mcg/kg/day (not to exceed 300 mcg/day. Filgrastim administration will continue daily until neutrophil count > 1.0 x10^9/L x 3 days or > 5.0 x10^9/L.
Intervention MeSH terms: Cyclophosphamide; Fludarabine; Interleukin-2; Monatide (IMS 3015)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 170.0
Sex: All
Minimum age: 7 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Immunotherapy; Adoptive Transfer; IL-2; Toxicity; Clinical Response; Breast Cancer

Summary:

      This experiment will test the safety and effectiveness of a treatment for melanoma in which
      certain lymphocytes (a type of white blood cell) are taken from the patient, grown in the
      laboratory, and returned after the patient's immune system has been weakened with
      immune-suppressing drugs. Some patients will also receive interleukin-2 (IL-2), a drug that
      may enhance the activity of the re-infused lymphocytes.

      Patients with metastatic melanoma (melanoma whose tumor has spread) who have been treated
      unsuccessfully with gp100 vaccination may participate in this study. They will undergo
      apheresis or a tumor biopsy, or both, to collect lymphocytes. In apheresis, whole blood is
      drawn through a needle in the arm. A machine separates the blood components and removes the
      white cells. The rest of the blood is returned to the donor through a needle in the other
      arm. A biopsy is a surgical procedure to remove a small piece of tumor tissue.

      Several weeks before the lymphocytes are collected, patients will receive injections of
      growth colony stimulating factor (G-CSF) every day for five days. This drug stimulates white
      cell production, permitting as many cells as possible to be obtained during collection. The
      lymphocytes will then be grown in larger numbers in the laboratory.

      Seven days before the cells are re-infused, the patient is admitted to the hospital and a
      catheter (small tube) is placed in a large vein in the chest or neck. Two drugs,
      cyclophosphamide and fludarabine, are given through the tube. These drugs suppress the immune
      system so that it will not interfere with the work of the reinfused lymphocytes. The
      lymphocytes are then injected through the catheter over a 30-minute period. After the
      infusion, patients who receive IL-2 will be given the drug in a high dose over a 15-minute
      period every eight hours for up to five days. Patients whose condition does not permit
      high-dose IL-2, such as those with a heart condition or lung problem, may receive a low-dose
      regimen, with the drug given as a shot under the skin of the thigh or abdomen for five days
      followed by a 2-day break, continuing for a total of six weeks. These patients receive a
      higher dose the first week and then half that dose the next five weeks.

      Blood and tissue samples will be taken before and during the study to evaluate the size of
      the tumor and assess treatment. If, 3-5 weeks after therapy is completed, the patient's tumor
      has stabilized or shrunk, the entire treatment, except for chemotherapy, may be repeated two
      more times.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

          -  Patients must have evaluable metastatic melanoma that is refractory to standard
             therapy.

          -  Age greater than or equal to 16 years.

          -  Patients of both genders must be willing to practice birth control for four months
             after receiving the preparative regimen.

          -  Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at entry
             to the trial and at the time of chemotherapy induction.

          -  Absolute neutrophil count greater than 1000/mm^3.

          -  Platelet count greater than 100,000/mm^3.

          -  Hemoglobin greater than 8.0 g/dl.

          -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than two
             times the upper limit of normal.

          -  Serum creatinine less than or equal to 1.6 mg/dl.

          -  Total bilirubin less than or equal to 1.6 mg/dl, except for patients with Gilbert's
             Syndrome who must have a total bilirubin less than 3.0 mg/dl.

          -  More than four weeks must have elapsed since any prior therapy at the time the patient
             receives the preparative regimen.

          -  Women of child-bearing potential must have a negative pregnancy test because of the
             potentially dangerous effects of the preparative chemotherapy on the fetus.

          -  Life expectancy of greater than three months.

          -  No steroid therapy required.

          -  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.

          -  Patients to receive high dose interleukin 2 (IL-2) must have no active systemic
             infections, coagulation disorders or other major medical illnesses of the
             cardiovascular, respiratory or immune system.

          -  Patients who will receive high dose IL-2 as part of the phase I portion of this study
             or who will be randomized must be eligible to receive high dose IL-2.

          -  Any patient receiving IL-2 must sign a durable power of attorney.