Chemotherapy Followed by gp100 Lymphocytes and Aldesleukin to Treat Melanoma
Condition: Skin Cancer; Metastatic Melanoma
MeSH terms: Melanoma; Skin Neoplasms
Intervention: Aldesleukin
Intervention description: High-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses).
Receive low-dose aldesleukin subcutaneously (SC) once daily 5 days a week for up to 6 weeks
Intervention MeSH terms: Aldesleukin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Malignant Melanoma; HLA-A2; Immunotherapy; Clinical Response; Skin Cancer

Summary:

      Background:

      This study uses a new experimental procedure for treating melanoma that uses the patient's
      own lymphocytes (type of white blood cell), which are specially selected to target and
      destroy their tumor.

      Objectives:

      To determine whether this experimental treatment can cause the patient's tumor to shrink.

      To test the safety of the treatment and its effects on the immune system.

      Eligibility:

      Patients with metastatic melanoma 18 years of age and older for whom standard treatments are
      not effective or who cannot take high-dose interleukin-2 (IL-2).

      Patients must have the tissue type human leukocyte antigens (HLA-A)0201.

      Design:

      Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.

      Patients have leukapheresis (a procedure for collecting lymphocytes that is similar to
      collecting whole blood) to collect cells for laboratory treatment and later reinfusion.

      Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to
      receive the cultured lymphocytes.

      Cell infusion and IL-2 treatment: Patients receive the lymphocytes by infusion through a vein
      and then either high-dose IL-2 infused through a vein or low-dose IL-2 injected under the
      skin. High-dose IL-2 is given as infusions through a vein every 8 hours for up to 15 doses.
      Low-dose IL-2 is given as injections under the skin daily for 5 days, followed by a 2-day
      rest, with this regimen repeated for a total of 5 weeks.

      Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and
      IL-2.

      Tumor biopsy: Patients may be asked to have a biopsy (removal of a small piece of tumor)
      after receiving treatment to look at the effects of treatment in the tumor.

      Follow-up: After treatment is completed, patients return to the clinic for physical
      examinations, review of side effects, laboratory tests and scans every 1 to 6 months until
      the disease worsens.

      Retreatment: Patients whose tumor did not grow after treatment or showed evidence of
      shrinking may be able to be retreated if their tumor begins to grow. They receive the same
      regimen of chemotherapy, lymphocyte infusion and IL-2 treatment....
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Measurable metastatic melanoma. The diagnosis of metastatic melanoma and positivity
             for gp100 will be confirmed by the Laboratory of Pathology of the the National Cancer
             Institute (NCI).

          2. Patients must be refractory to high dose aldesleukin treatment if they are medically
             eligible to receive it. Patients with noncutaneous melanoma are not required to be
             refractory to high dose aldesleukin.

          3. gp100:154-162 reactive peripheral blood lymphocytes derived from a

             leukapheresis.

          4. HLA-A*0201 positive.

          5. Greater than or equal to 18 years of age.

          6. Willing to practice birth control during treatment and for four months after receiving
             the preparative regimen.

          7. Life expectancy of greater than three months.

          8. Willing to sign a durable power of attorney.

          9. Able to understand and sign the Informed Consent Document.

         10. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 for
             the high dose aldesleukin cohort or ECOG 0, 1 or 2 for the low dose aldesleukin
             cohort.

         11. Hematology:

               -  Absolute neutrophil count greater than 1000/mm^3 without support of filgrastim

               -  Normal white blood cell (WBC) (greater than 3000/mm^3).

               -  Hemoglobin greater than 8.0 g/dl

               -  Platelet count greater than 100,000/mm^3.

         12. 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 or hepatitis C.

         13. Chemistry:

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than
                  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 2.0 mg/dl, except in patients with
                  Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.

         14. Negative pregnancy test in women of child bearing potential because of the potentially
             dangerous effects of the preparative chemotherapy on the fetus.

         15. 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).
             Patients may have undergone minor surgical procedures within the past 3 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.

         16. Six weeks must have elapsed since prior cytotoxic T-lymphocyte antigen 4 (anti-CTLA4)
             antibody therapy to allow antibody levels to decline.

         17. Patients who have previously received anti-CTLA4 antibody and experienced treatment
             must have a normal colonoscopy with normal colonic biopsies.

        EXCLUSION CRITERIA:

          1. 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.

          2. Systemic steroid therapy required.

          3. For patients receiving high dose IL-2 only: 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.

          4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
             Disease).

          5. 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.)

          6. History of severe immediate hypersensitivity reaction to any of the agents used in
             this study.

          7. The following patients will be excluded from the high-dose IL-2 arm (but will be
             eligible for the low-dose arm):

               1. History of coronary revascularization or ischemic symptoms

               2. Any patient known to have an left ventricular ejection fraction (LVEF) less than
                  or equal to 45%.

               3. Documented LVEF of less than or equal to 45% tested in patients with:

                    -  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

               4. Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted
                  tested in patients with:

                    -  A prolonged history of cigarette smoking (20 pk/yrs of smoking)

                    -  Symptoms of respiratory dysfunction